Immunocytochemical evidence of histamine 1 and histamine 2 receptors on mice sperm

Histamine is a biogenic amine which is synthesised by L-histidine decarboxylase enzyme (HDC). The histamine 1 and 2 antagonist administrations have been highly reported to cause detrimental effect on sperm parameters, which arisen the speculation of histamine 1 (H1R) and histamine 2 (H2R) receptors might be present in sperm. The present study was aimed to provide evidence on the localisation of H1R and H2R on mice sperm through immunocytochemistry. The sperm was harvested from cauda epididymis. After one hour of incubation, sperm suspension was smeared onto a poly-lysine-coated slide and allowed to dry before fixation and permeabilisation processes. The primary antibody encoded for receptors was exposed to the fluorescently tagged antibody; fluorescein isothiocyanate (FITC) conjugate followed by nuclear staining with 4?, 6-diamino-2-phenylindole dihydrochloride (DAPI). The testis, stomach, and skin were used as the positive controls. Our data showed that both receptors have been expressed on the midpiece and acrosome of mice. The present result was the first discovery of the presence and immunolocalisation of H1R and H2R on mice sperm. Therefore, present study proposes that these receptors could be involved in calcium regulatory mechanism and protein phosphorylation which are responsible for fertilisation-related processes.

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.

Antihistamínicos Parte II - ¿Cuáles son las opciones y en qué basarse para elegir la mejor? / Antihistamines Part II - What are the options and how to choose the best?

Los antihistamínicos han sido usados durante los últimos 50 años y se han convertido en los medicamentos de mayor prescripción en el mundo. En este artículo se revisa el desarrollo de nuestro conocimiento referente a la histamina en el transcurso del siglo, como mediador biológico almacenado y liberado mayormente por los basófilos y mastocitos; mediador biológico situado en diferentes tejidos corporales, y otras células, con un papel fisiológico fundamental en el control de la secreción de ácido gástrico y un papel fisiopatológico en una gama de trastornos alérgicos. La síntesis y estudios farmacológicos de agonistas y antagonistas selectivos han establecido la existencia de cuatro tipos de receptores de histamina y antagonistas de ellos, que han encontrado muy importantes aplicaciones terapéuticas. Debido al aumento de la prevalencia de las enfermedades alérgicas según el Libro Blanco de Alergia (WAO), se deben crear normas que promuevan el uso de los antihistamínicos de manera adecuada y racional. De esta manera, la correcta elección debe ser realizada de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones particulares en pacientes con algún riesgo incrementado. El crear normas que promuevan una práctica terapéutica óptima o uso racional de dichos medicamentos. Elegirlos de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones especiales en pacientes portadores de ciertas enfermedades de riesgo a utilizarlos.(AU)

Antihistamines have been used for the past 50 years and have become the most prescribed drugs in the world. This article reviews the development of our knowledge concerning the histamine in the course of the century, as a biological mediator mostly stored and released by basophils and mast cells biological mediator located in different body tissues, and other cells, having a fundamental physiological role in the control of gastric acid secretion and pathophysiological role in a variety of allergic disorders. The synthesis and pharmacological studies of selective agonists and antagonists has established the existence of four types of histamine receptor antagonists and histamine receptor found important therapeutic applications. Power demonstrations relate most allergic diseases whose symptoms are chronic and persistent emphasis by (WAO) White Paper on Alergia1 a steady increase in allergic diseases with a prevalence of 30-40% of the world population affected at least one allergic condition, considering the most common allergic rhinitis and chronic diseases common in our modern society. Creating standards that promote optimal therapeutic practice or rational use of such drugs. Choose them according to their efficacy, tolerability, safety, age group, situations and special precautions in patients with certain diseases risk to use. (AU)

Characteristics in Molecular Vibrational Frequency Patterns between Agonists and Antagonists of Histamine Receptors

To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.

Revisão sobre a efícacia e segurança dos anti-histamínicos de primeira e segunda geração / Revision on efficacy and safety of antihistamines of first and second generation

Objetivo: Revisar a eficácia e segurança dos principais anti-histamínicos de primeira e segunda geração. Os anti-histamínicos correspondem a um grupo extenso de medicamentos que vêm apresentando grandes avanços no conhecimento de suas ações e estão entre os agentes mais utilizados na prática clínica em diversas doenças alérgicas. Método: Levantamento bibliográfico nos bancos de dados PubMed, Medline, LILACS, SCIELO e capítulos de livros nos últimos 10 anos, sendo incluídos artigos históricos. Resultados: Nessa revisão são destacadas as principais características da histamina, as diferenças entre os receptores de histamina, o desenvolvimento dos anti-histamínicos de primeira e segunda geração, sua classificação e os principais efeitos colaterais de cada grupo de anti-histamínicos. Conclusão: A presente revisão não pretende esgotar o assunto sobre eficácia e segurança dos anti-histamínicos, mas destaca a falta de estudos bem conduzidos sobre eficácia dos anti-histamínicos de primeira geração e o número crescente de metanálises sobre farmacodinâmica, potência, eficácia e segurança dos anti-histamínicos de segunda geração.

Objective: To review the efficacy and safety of the main antihistamines of first and second generation. The antihistamines represent an extensive group of drugs that are showing great advances in knowledge of their actions and are among the most common agents used in clinical practice in various allergic diseases. Method: Searches in PubMed, Medline, LILACS, SCIELO database and book chapters in the last 10 years, including historic articles. Results: This review highlights the main features of histamine, the differences between histamine receptors, development of first and second generation antihistamines, their classification, and the main side effects of each group of antihistamines. Conclusion: The present review is not intended to exhaust the subject on efficacy and safety of antihistamine, but it highlights the lack of well conducted studies of the efficacy of first-generation antihistamine and the rising number of meta-analysis of pharmacodynamics, potency, efficacy and safety of second-generation antihistamines.

El ácido gástrico / Gastric acid

El ácido gástrico, producto de la secreción de las células gástricas parietales u oxínticas, cumple roles biológicos imprescindibles para la homeostasis corporal. La producción del ácido gástrico depende de un proceso celular efector constituido por histamina, acetilcolina y gastrina en el primer nivel, constituyendo primeros mensajeros de dicho proceso. Estos interaccionan con receptores específicos, lo que a su vez activa segundos mensajeros representados por AMPc y el sistema calciocalmodulín. Estos luego activan en cascada sucesiva a una proteinokinasa que fosforila una proteína específica, activándola, lo que inicia la síntesis de ácido. Una bomba de protones situada en el polo luminal de la célula parietal, extruye finalmente el ácido sintetizado hacia el lumen gástrico. El proceso secretor descrito es puesto en movimiento, secuencialmente en tres fases, dos de ellas estimuladoras -fase cefálica y fase gástrica- y una inhibidora o fase intestinal. Estas etapas son iniciadas por fenómenos sico-neurales -pensamiento, visión, olfación o recuerdo-; por alimentos y otras sustancias ingeridas; y por productos de la digestión de nutrientes. Alteraciones en la regulación de la secreción ácida; en la constitución de la barrera mucosa gastroduodenal, protectora frente a la acción potencialmente lesiva de alimentos y fármacos o drogas; y potenciación de su acción por la presencia de H. pylori, constituyen la base etiopatogénica de la enfermedad ácido-péptica, entidad nosográfica donde juega un rol fundamental. Desde el punto de vista terapéutico, tanto dentro del marco teórico como del práctico, se puede interferir con la secreción ácida neutralizando alguno de los pasos de su proceso celular efector. Un adecuado conocimiento de los aspectos básicos relacionados con la problemática del ácido gástrico, permite plantear estrategias para el manejo de la patología asociada con él, en forma particular en lo concerniente a la enfermedad ácido-péptica en todas...

Gastric acid, a product of parietal cells secretion, fullfills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressively activated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, ¡t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms.

The role of H1- and H2-receptors in the effect of compound 48/80 in the asphyxiation and body temperature of mice

Contribution of histamine H1- and H2-receptors to the effect of compound 48/80, a potent histamine releaser, upon asphyxiation and body temperature in mice was investigated in the present experiments. Compound 48/80 showed an apparent protective potency against hypoxia and significantly prolonged the latencies for convulsions and death in a dose-dependent manner. Compound 48/80 also decreased the body temperature, which was in relation with the antihypoxic effect. Both the H1-receptor antagonist, dimethindene, and the H2-receptor antagonist, ranitidine, attenuated the hypothermic effect of compound 48/80, indicating the involvement of central histamine through both the H1- and H2-receptors. Ranitidine had no effect on the protective effect of compound 48/80 against hypoxia-induced lethality, whereas dimethindene completely antagonized it. These results suggest that the protective effect of compound 48/80 against hypoxia is mediated through histamine H1-receptors and is not related to its ability to induce hypothermia.