Histamine Excites Rat GABAergic Ventral Pallidum Neurons via Co-activation of H1 and H2 Receptors / 神经科学通报·英文版

The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.

Cleansing the world of the germ of laziness: hygiene, sanitation, and the Javanese population in Suriname / Limpando o mundo do germe da preguiça: higiene, saneamento e população javanesa no Suriname

In 1915 the Rockefeller Foundation took its hookworm eradication campaign to Suriname, but was soon disappointed because of opposition from its main target group: the Javanese. Moreover, authorities and planters objected to the construction of latrines because of the costs and their belief that the Javanese were “unhygienic”. In describing the labor migration from Java to Suriname, I show that this “lack of hygiene” was closely related to the system’s organization. I argue that uncleanliness was the consequence of harmful socio-economic and ecological conditions. Secondly I suggest that even though the Foundation did not manage to cleanse Suriname of hookworm, its educational efforts, its emphasis on prevention, and its training of local health workers probably had more impact than Rockefeller officials thought.

Em 1915, a Fundação Rockefeller levou sua campanha de erradicação da ancilostomíase ao Suriname, logo sofrendo a oposição de seu principal alvo, os javaneses. Autoridades e proprietários rurais também reagiram à instalação de latrinas devido aos custos implicados e à crença de que os javaneses eram “anti-higiênicos”. Ao descrever a migração de trabalhadores de Java para o Suriname, mostro que a “falta de higiene” ligava-se à organização do sistema. Argumento que a sujeira era consequência de condições ecológicas e socioeconômicas danosas. Sugiro ainda que, embora a Fundação não tenha livrado o Suriname da anciolostomíase, seus esforços educacionais, sua ênfase na prevenção e o treinamento de profissionais de saúde locais tiveram maior impacto do que o imaginado pelos funcionários da agência norte-americana.

The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (alpha-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with alpha-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, alpha-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine

Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca2+ influx and Ca2+ release from internal stores in a PLC and PLD dependent manner.

Two Clinical Manifestations of Anterior Segment Associated with Systemic Lupus Erythematosus

PURPOSE: To report the clinical course and results of two cases of anterior segment manifestations associated with systemic lupus erythematosus (SLE). CASE SUMMARY: The first case was a 63-year-old female patient who was diagnosed with corneal ulcer and symblepharon on her left eye and dry eye in both eyes. Although the patient was treated with topical antibiotics, autologous serum and artificial tears, amniotic membrane transplantation and symblepharon removal were subsequently required. At 1 month after medical and surgical treatment, the corneal ulcer improved, but a descemetocele was formed because of persistent corneal thinning. The second case was a 24-year-old female patient diagnosed with filamentary keratitis and recurrent corneal erosion in both eyes and uveitis in her left eye. After treatment with therapeutic contact lenses, topical antibiotics and steroids, her symptoms were slightly improved. After 6 months of treatment, filamentary keratitis and corneal erosion recurred to being intractable. The patient received systemic evaluation and was diagnosed with SLE. After a combined therapy of oral and topical treatments, filamentary keratitis and recurrent corneal erosion improved significantly. CONCLUSIONS: Clinical manifestations of anterior segment associated with SLE rarely respond to topical treatment and are apt to recur easily; therefore, systemic treatment should be applied for better prognosis. Thus, the therapeutic strategy in intractable ocular diseases should be designed with consideration of accompanying systemic diseases.

Neonatal Coagulation Disorder: Diagnostic Approaches for Bleeding Neonates

All newborn infants with clinically significant bleeding should be evaluated for a hemostatic deficit. Medical history should include the following data: familial bleeding disorders, maternal illness and medication, age of bleeding onset, and prophylactic administration of vitamin K. The first essential step for evaluating bleeding neonates is determining whether the baby is sick or well. The physician should also evaluate the extent of the bleeding, features of bleeding lesions, and other abnormal findings from the physical examination. Skeletal anomalies may provide diagnostic clues. Depending on the clinical features and results of screening tests, other tests including coagulation factors may be useful for determining the diagnosis. All laboratory results must be considered in the context of age-related reference values. The platelet function analyzer provides a promising alternative to bleeding time. Fibrin degradation products and D-dimers are used for screening and specially testing fibrinolytic activity, respectively. The Apt test may help to rule out factors derived from maternal blood. Radiologic imaging studies are important because asymptomatic intracranial hemorrhages are common in neonates.

The Present and Future of Molecular Epidemiology in Tuberculosis

Molecular epidemiology has been initiated for the confirmation of transmission link among tuberculosis patients. IS6110 restriction fragment length polymorphisms (RFLP) technique has been used as an excellent tool to discriminate Mycobacterium tuberculosis isolates, especially in tuberculosis (TB) outbreak in the population. IS6110 RFLP has the most discriminatory power for the M. tuberculosis isolates with high copy number of IS6110 like Korean isolates. Spoligotyping using spacers of direct repeat is useful to distinguish Beijing strains which are found widely in Eastern Asia, from non-Beijing strains. It is known that Beijing strains are more virulent, apt to be drug resistant than non-Beijing strains. Strain typing techniques of Mycobacterium tuberculosis has lead to the development of phylogenetic classification. Variable number tandem repeat (VNTR) of M. tuberculosis is another good target for strain typing. The technique using VNTR is rising as an alternative tool to overcome disadvantages of IS6110 RFLP which is time consuming in the sense that it takes longer time to process from the culture positive bacilli, and has the intrinsic difficulties in objectification of the results. The combination of many VNTR loci enhances discriminatory power to become equal to that of IS6110 RFLP. On the other hand, the optimal VNTR combination differs from one country to another due to different dominant clade. Large sequence polymorphisms (LSP) and single nucleotide polymorphisms (SNP) are important tools for the classification of the phylogeny of M. tuberculosis complex. Many previous reports indicate that the depending upon the type of strains, the ways of transmission of disease, the way to get infected with disease and the development of drug resistance conditions are variable. Therefore, the molecular epidemiology of M. tuberculosis has become more important for tuberculosis control in the world. It will be possible to set up tuberculosis-tailored policy after the characterization of M. tuberculosis by molecular epidemiologically.

Lung Cancer Associated with Sarcoidosis: A case report

Sarcoidosis is a somewhat common pulmonary disease, but the concurrence of lung cancer and sarcoidosis in the same patient is very rare. Because sarcoidosis usually presents as mediastinal lymphadenopathies, this concurrence in a lung cancer patient detected radiologically is apt to be misunderstood to be mediastinal metastases, and it is thus considered to be an unresectable disease. We report a case of lung cancer associated with sarcoidosis that developed in a 65-year-old woman who underwent surgery. Radiological studies revealed a 1.9x1.7 cm mass in the left upper lobe with multiple enlarged bilateral mediastinal lymph nodes (2R, 3a, 4R, 4L, 5, 6, 7, 8R). Pathologic findings showed that the mass was a well-differentiated adenocarcinoma and all of the enlarged mediastinal lymph nodes were granulomas without cancer metastasis. We report this case with a review of the literature.

Lung Cancer Associated with Sarcoidosis: A case report

Sarcoidosis is a somewhat common pulmonary disease, but the concurrence of lung cancer and sarcoidosis in the same patient is very rare. Because sarcoidosis usually presents as mediastinal lymphadenopathies, this concurrence in a lung cancer patient detected radiologically is apt to be misunderstood to be mediastinal metastases, and it is thus considered to be an unresectable disease. We report a case of lung cancer associated with sarcoidosis that developed in a 65-year-old woman who underwent surgery. Radiological studies revealed a 1.9x1.7 cm mass in the left upper lobe with multiple enlarged bilateral mediastinal lymph nodes (2R, 3a, 4R, 4L, 5, 6, 7, 8R). Pathologic findings showed that the mass was a well-differentiated adenocarcinoma and all of the enlarged mediastinal lymph nodes were granulomas without cancer metastasis. We report this case with a review of the literature.

Amiodarone-induced Pulmonary Toxicity within a Short Period of the Initiation of Amiodarone Therapy: A Case Report / 대한구급학회지

Amiodarone is one of the most commonly prescribed antiarrhythmic drug for almost all atrial or ventricular arrythmias. Amiodarone-induced pulmonary toxicity (APT) was first described in 1980 and has potentially serious side effects that are believed to develop in 5% of patients. In general, APT occurs only when high amiodarone doses are used for a long time. However, during short-term therapy of amiodarone, APT is rarely reported. In this report, we describe a case of amiodarone-induced pulmonary toxicity after a short course of amiodarone therapy for atrial fibrillation.

Clinical Results of Wavefront-guided LASIK

PURPOSE: To investigate and compare the clinical outcomes of wavefront-guided LASIK performed by 2 different laser platforms. METHODS: A retrospective analysis of consecutive cases of eyes that underwent wavefront-guided LASIK by using the VISX S4 CustomVue system and the Zyoptix Z100 system advanced personalized mode. All procedures were performed by one surgeon. Fifty-six eyes of 36 patients were included. Of the 56 eyes, 30 eyes underwent LASIK by using the VISX S4 CustomVue system (CustomVue group), and other 26 eyes underwent LASIK by using the Zyoptix Z100 system (APT group). Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction, contrast sensitivity, total high order aberration (HOA), spherical aberration (SA) and Q-value were recorded preoperatively and at 1 week, 1 and 3 months postoperatively. RESULTS: There was no statistically significant difference between two groups in terms of preoperative UCVA, BCVA, manifest refraction, high order aberrations, Q-value and contrast sensitivity. Induced amount of SA was significantly lower in CustomVue group than in APT group (p = 0.02). CONCLUSIONS: Wavefront-guided LASIK performed by 2 different laser platforms caused clinically acceptable outcomes including good visual acuity and contrast sensitivity through 3 months. Furthermore, LASIK performed by VISX S4 CustomVue system caused less SA at three months after operation.

Development of Novalis Quality Assurance Protocol for Radiosurgery / 의학물리

In Republic of Korea, there are many Quality Assurance protocol for general radiation treatment machine such as linac. However, Quality Assurance protocol for radiosurgery treatment system is not ready perfectly. One of the radiation treatment machine for radiosurgery, novalis system needs to suitable Quality Assurance protocol for using it right way during radiation treatment and maintaining suitable accuracy for daily, weekly, monthly and annually periods. Therefore, in this article, we develop Quality Assurance protocol for novalis system. We collected and analysed domestic and foreign novalis Quality Assurance protocol. After that, we selected essential QA items and each tolerance range for developing proper QA protocol, and we made anatomical phantom for execution of selected QA items and evaluation of overall state of QA, and then, we use this measured value as a reference. Quality Assurance items are consisted of Mechanical accuracy QA part and Radiation delivery QA part. Mechanical accuracy QA part is comprised of radiation generation machine part, assistive devices part and multi-leaf collimator part. Radiation delivery QA part is divided into radiation isocenter accuracy and dosimetric evaluation. After that, developed novalis QA tables are made by using these QA items. These novalis QA tables would be used to good standard in order to maintain apt accuracy for radiosurgery in daily, weekly, monthly and annually periods.

In-Stent Stenosis of Stent Assisted Endovascular Treatment on Intracranial Complex Aneurysms

OBJECTIVE: To introduce the frequency and segment analysis of in-stent stenosis for intracranial stent assisted endovascular treatment on complex aneurysms. METHODS: A retrospective study was performed in 158 patients who had intracranial complex aneurysms and were treated by endovascular stent application with or without coil embolization. Of these, 102 patients were evaluated with catheter based angiography after 6, 12, and 18 months. Aneurysm location, using stent, time to stenosis, stenosis rate and narrowing segment were analyzed. RESULTS: Among follow-up cerebral angiography done in 102 patients, 8 patients (7.8%) were shown an in-stent stenosis. Two patients have unruptured aneurysm and six patients have ruptured one. Number of Neuroform stents were 7 cases (7.5%) and Enterprise stent in 1 case (11.1%). Six patients demonstrated in-stent stenosis at 6 months after stent application and remaining two patients were shown at 12 months, 18 months, respectively. CONCLUSION: In-stent stenosis can be confronted after intracranial stent deployment. In our study, no patient showed symptomatic stenosis and there were no patients who required to further treatment except continuing antiplatets medication. In-stent stenosis has been known to be very few when they are placed into the non-pathologic parent artery during the complex aneurysm treatment, but the authors found that it was apt to happen on follow up angiography. Although the related symptom was not seen in our cases, the luminal narrowing at the stented area may result the untoward hemodynamic event in the specific condition.

Diagnostic Usefulness of the Serum-Specific IgE, the Skin Prick Test and the Atopy Patch Test Compared with That of the Oral Food Challenge Test

BACKGROUND: Atopic dermatitis (AD) is frequently associated with food allergies. In addition to the skin prick test (SPT) and serum-specific IgE, the atopy patch test (APT) has been introduced as a diagnostic procedure for food allergies. OBJECTIVE: Our aim was to evaluate the diagnostic value of the APT, the SPT and the serum-specific IgE levels compared with that of oral food challenge test against milk and egg in AD patients. METHODS: We conducted the SPT and APT, and determined the serum-specific IgE levels against milk and egg antigens for 101 patients. Oral food challenge tests were conducted for 86 out of 101 AD patients. The sensitivity, specificity and positive and negative predictable values were calculated for all the tests. RESULTS: Twenty-five patients were positive to oral food challenges. The sensitivity of the APT for milk was 66.7%, while the figures for the SPT and the serum-specific IgE were 35.5% and 14.2%. The sensitivity of the APT for egg was 50%, while that for the SPT and serum-specific IgE were 21.4% and 6.7%. CONCLUSION: We were able to conclude that the APT test seems to be a valuable additional tool for the diagnostic method of food allergies in AD.

A Novel Technique for Retrieval of a Drug-Eluting Stent After Catheter Break and Stent Loss

Break of a stent delivery catheter and subsequent stent loss (SL) has been a rare event in the drug-eluting stent (DES) era. We here report a case of successful retrieval of a stent after a break if the delivery catheter and SL from a balloon catheter at a culprit lesion. We finally resolved this situation using a simple balloon technique for both the broken stent catheter inside of the guide catheter and the unexpanded stent in the culprit lesion. Thus balloons are an important weapon in our armamentarium in the cardiac catheterization laboratory for urgent retrieval of a lost stent. Their apt use definitely allowed our patient to avoid undergoing emergency cardiovascular thoracic surgery.

Effect of Residential Environment on the Health Status in Apartment Inhabitants / 農村醫學 地域保健

OBJECTIVES: WHO insisted on that we should study about association between residential environment and health status and make 'health city' concept as practical motto. This study analyzed about that how community environment affected their health. METHODS: We surveyed residential environment satisfaction and health status of a apartment complex residents. We transformed Chun's index about housing environment study and social capital index of WHO and used as community health survey. We analyzed the association between health status and related factor by using principal compound analysis and logistic regression analysis. RESULTS: We found out that the perceived health status 1 years ago was highly related to the residential environment and also extracted five residential environment component (APT maintenance, House, APT complex, Neighbor, APT building) by principal component analysis. After residential environment component, demographic and socioeconomic variable were controlled, the high satisfaction group of APT complex and neighbor relationship was in lower risk of perceived health status 1 years ago than the low satisfaction group. CONCLUSIONS: Recently, the importance of residential environment and neighborhood is shaped as community capacity. Therefore, social relationship and residential environment should be the core variable for health promotion of community. After all, we should know the relationship of residential environment and perceived health status 1 years ago. This helps the concept of health city clearly.

Atopy Patch Tests for Atopic Dermatitis Patients according to the Concentration and Vehicle for the Cockroach Antigen / 대한피부과학회지

BACKGROUND:Recent studies have attempted to document the correlation of an atopy patch test (APT) and a skin prick test. The results have suggested a possible role of delayed allergic reaction in the development of eczematous skin lesions in patients with atopic dermatitis (AD) OBJECTIVE: The aim of this study was to evaluate the relationship of APT with skin prick test and specific IgE for cockroach antigen. And we attempted to find the optimal vehicle and concentration of APT for cockroach allergy in AD patient. METHODS: We performed APTs in 50 patients with AD with using German cockroach allergens (the extract with different concentrations and vehicles). The reactions were evaluated after 48 hours, and these were compared with the results of the skin prick test and the total and specific IgE levels. RESULTS: The AD patients who had cockroach allergy, according to a skin prick test or the specific IgE level, showed higher positive APT reactionsthan the non-allergic patients to cockroach. The APT reactions showed a significant relationship with the skin prick test and the specific IgE level (85.7%). With regard to the form of cockroach antigen, a positive APT was more frequent with using the powder form that with using the extract. Regarding the vehicle, petrolatum induced higher positive APT reactions than did distilled water. There was a close relationship between the antigen concentration in petrolatum base and a positive APT reaction. Ten and fifty percent cockroach antigen elicited positive APT reactions than did 1% cockroach antigen with using a petrolatum base. CONCLUSION: Petrolatum is an optimal vehicle for an APT for cockroach because an APT with a petrolatum base revealed the highest correlation with cockroach allergy. The dose-response relationship between antigen concentration and the frequencies of positive APT reactions demonstrated that 10% and 50% cockroach antigen is superior to 1% cockroach antigen.

Febrile Seizures after 5 Years of Age : Clinical and Electroencephalographic Characteristics / 대한간질학회지

PURPOSE: We aimed to investigate the electroclinical characteristics of patients having persistent seizures with fever after 5 years of age, which has not been elucidated well. METHODS: We identified 101 patients over 5 years (M : F=64 : 37, range: 5.0-11.0), visited our hospital for febrile seizure. Their medical records for clinical features and EEG findings at last seizure were retrospectively reviewed. RESULTS: The mean onset age of seizure of total patients was 3.0 years (range: 0.3-8.3). The complex features were noted in 15.8%. Family history were in 53.3%. Neurologic abnormalities were in 10.9%. Abnormal EEGs were in 36.7% (generalized spike or polyspike-waves: 10, focal epileptic discharges: 16, others: 3). When we compare the patients of 5.0-5.9 years (Group A, n=48) to the patients after 6 years (Group B, n=53), complex features (20.8% vs 37.8%, p=0.063) and AED treatments (6.3% vs 18.9%, p=0.059) were more common in Group B. Among group B, patients after 8 years were more apt to be treated by AED than youngers (6.1% vs 40.0%, p=0.002). When we compare the patients starting their first seizure before 5.0 years (Group C, n=78) to the patients after 5.0 years (Group D, n=23), Group C had more frequent seizures (6.6 vs 2.3, p= < 0.0001) and family history (58.3% vs 25.0%, p=0.039). Group D had more common abnormal neurologic findings (7.7% vs 21.7%, p=0.057). CONCLUSION: Febrile seizures in older age group are more associ-ated with complex features, EEG abnormalities and AED treatments. The patients with seizure onset before 5.0 years had more seizure frequency and family histories.

Anatomical Evaluation of Extraocular Muscles and Relationships Among Macula and Optic Nerve in Enucleated Eye

PURPOSE: To make an anatomical evaluation of extraocular muscles, macular and optic nerve in enucleated eyes of live subjects and to compare the results with a previous autopsy study. METHODS: Twenty-four surgically enucleated eyes were studied. The distance from the limbus to the muscle insertion site, muscle width, and the distance between muscle insertion sites were measured and compared with an Apt study. After an incision through the eyeball, a 26-gauge needle was passed perpendicularly through the macula to the sclera. We measured the distances between the oblique muscles and the macula and optic nerves from an external site of the eyeball. RESULTS: The distance from the limbus to the muscle insertion site showed a significant difference in the superior and inferior rectus muscle. All measurements of muscle widths were significantly narrower than those of autopsy studies. The distances between the muscles were significantly closer between the lateral and superior muscles and between the superior and medial rectus muscles. From the optic nerve to the muscle was 3.99+/-0.62 mm, to the superior oblique muscle was 7.89+/-0.88 mm, to the inferior oblique muscle was 5.95+/-0.83 mm, and the macula to the inferior oblique muscle was 1.35+/-0.42 mm. CONCLUSIONS: Since most of the measurements were different from those of autopsy studies, we should consider the effects of preservation and fixation solution on autopsy eyes, race, and the differences among measurement instruments.

Effects of histamine H|2-receptor stimulation on Mg2+ efflux in perfused guinea pig heart

Mg2+ is an important regulator of many cardiac functions. However, regulation of intracellular Mg2+ activity in the heart is not well characterized. To assess the effect of histamine H2-receptor stimulation on intracellular Mg2+ regulation, changes in extracellular Mg2+ concentration were examined under a variety of conditions in perfused guinea pig hearts. Mg2+ in the cardiac perfusate was measured by atomic absorbance spectrophotometry. The histamine (10(-6) M induced a marked Mg2+ efflux from the heart. The H2-receptor antagonists, cimetidine (10(-5) M), ranitidine (10(-5) ND, but not a H1-receptor antagonist, diphenhydramine (3 X 10(-6) M), completely blocked the histamine-induced Mg2+ efflux. The Mg2+ efflux could also be induced by forskolin (3 X 10(-6) M), 8-Cl-cAMP (2 X 10(-4) M), permeable cAMP analogue, or dimaprit, (10(-5) M). However, the carbachol (10(-5) M) considerably decreased the efflux of Mg2+. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, dimaprit-induced Mg2+ efflux was potentiated. These results suggest that a significant Mg2+ efflux from perfused guinea pig heart by histamine can be induced by the histamine H2-receptor stimulation and it is suggested that cytosolic cAMP may be linked.