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1.
Phys Rev Lett ; 132(23): 233002, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38905657

ABSTRACT

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

2.
BJA Educ ; 21(11): 414-419, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34707886
3.
J Rheumatol ; 27(10): 2351-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11036829

ABSTRACT

OBJECTIVE: The recommended reference range for serum C-reactive protein (CRP) concentrations is usually not adjusted for age and sex. We sought to determine if age, sex, and race or ethnicity influence the distribution of CRP values, and if upper reference limits of CRP should be adjusted by demographic factors. METHODS: Interviews, physical examinations, and blood draws were performed on > 22,000 individuals age > or = 4 yrs representative of the noninstitutionalized population of the United States, as part of the Third National Health and Nutrition Evaluation Survey (NHANES III). Serum CRP concentrations were measured by nephelometric immunoassay. RESULTS: The 95th percentile value of CRP in the overall population was 0.95 mg/dl for males and 1.39 mg/dl for females, and varied with age and race. For ages 25-70 yrs, the age adjusted approximate upper reference limit (mg/dl) was CRP = age/50 for males, and CRP = age/50 + 0.6 for females. The upper limits for Mexican-Americans and non-Hispanic whites were similar, whereas for non-Hispanic black adults the approximate upper limit was CRP = age/30 for males and CRP = age/50 + 1.0 for females. Even after accounting for identified inflammatory conditions, demographic factors influenced the reference limits of CRP. The 95th percentile values were uniformly lower in children than in older adults. CONCLUSION: Demographic factors, including age, sex, and race, should be used to adjust the upper reference limit for CRP. Clinicians should be aware of these factors when using CRP values to assess inflammatory diseases.


Subject(s)
Age Distribution , C-Reactive Protein/genetics , Racial Groups/genetics , Reference Values , Sex Distribution , Adolescent , Adult , Aged , Black People , C-Reactive Protein/analysis , Child , Child, Preschool , Female , Humans , Male , Mexican Americans/statistics & numerical data , Mexico/ethnology , Middle Aged , United States/epidemiology , White People
5.
Clin Chem ; 41(12 Pt 1): 1730-7, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7497613

ABSTRACT

Equivalence between Hybritech Tandem and Abbott IMx PSA methods have been reported by some but not all previous investigators. To determine reasons for these differing conclusions, we measured serum PSA with three different lots each of IMx and Tandem-E kits. Overall, mean IMx results were significantly lower than Tandem-E results; however, for selected sera, the IMx results were consistently higher than the Tandem-E results. Lot-to-lot differences for the IMx method were significantly greater than those with the Tandem-E method. Most IMx/Tandem-E lot-to-lot comparisons had linear regression slopes that differed significantly from 1.0, but some did not. Conclusions concerning the equivalence of the IMx and the Tandem-E methods can be influenced both by variations in the proportions of free PSA in sera in tested populations and by lot-to-lot differences in the IMx method.


Subject(s)
Prostate-Specific Antigen/blood , Humans , Male , Reagent Kits, Diagnostic , Regression Analysis
6.
Prostate ; 27(1): 1-6, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7541527

ABSTRACT

Consistency and reproducibility of serum prostate-specific antigen (PSA) measurement are essential in the application of this analyte to early detection or screening programs. In the present investigation, we sought to compare serum PSA levels determined by the IMx assay (Abbott Laboratories, North Chicago, IL) and the Tandem E (Hybritech Inc., San Diego, CA) to determine whether there were differences. Two hundred twenty-eight random sera from our archival bank were investigated. One hundred-eight specimens were in the Tandem range of 2.0-10.0 ng/ml, and prostatic histology was known based on either systematic sector needle biopsy or transurethral resection. PSA was measured with three different lost of the IMx and Tandem assays. Over the entire range, there was a good correlation (r2 = 0.985); however, in the more useful clinical range of 2.0-10.0 ng/ml, the correlation was reduced to 0.923; in the 2.0-6.0 ng/ml range, it was further reduced to 0.852. The slope for the entire range was 0.948; however, in the 2.0- to 10.0-ng/ml range, it was 0.894; in the 2.0- to 6.0-ng/ml range, the slope was 0.815. Using PSA cutoffs of 4.0, 5.0, and 6.0 ng/ml, significant decrease in abnormal PSA values in men with cancer was observed with the IMx compared with Tandem. These data suggest that the IMx and the Tandem PSA assays are not equivalent, and in most patients a lower value is realized with the IMx assay. This bias appears to be greater in men with prostate cancer. Clinicians must be aware which assay their patients are being tested with, and laboratory technicians should run internal standards to ensure lack of significant intralot variability and consistency over time.


Subject(s)
Prostate-Specific Antigen/blood , Reagent Kits, Diagnostic , Humans , Male , Prostatic Neoplasms/blood , Prostatic Neoplasms/prevention & control , Reproducibility of Results
7.
Neuropeptides ; 27(3): 175-83, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7816188

ABSTRACT

Changes in intracellular levels of free [Ca2+]i were monitored in cell suspensions and either single cells or cell clusters of the rat pancreatic tumour cell line AR42J grown on cover slips. Increases in free [Ca2+]i were seen when the bathing medium contained cholecystokinin octapeptide sulphated (CCK) or CCKB receptor agonists. Responses to CCK agonists were repeatable and reversed on washout. The responses to cholecystokinin and pentagastrin could be blocked by selective CCKB receptor antagonists but not a CCKA receptor antagonist. Depleting internal Ca2+ stores with thapsigargin blocked the response to pentagastrin suggesting that the response was mediated by Ca2+ release from internal stores. The rapid run down of the pentagastrin response in the absence of extracellular Ca2+ shows that replenishment of internal stores by extracellular Ca2+ is important in maintaining the CCK response.


Subject(s)
Calcium/metabolism , Cholecystokinin/pharmacology , Receptors, Cholecystokinin/metabolism , Animals , Benzodiazepinones/pharmacology , Bridged-Ring Compounds/pharmacokinetics , Cholecystokinin/antagonists & inhibitors , Devazepide , Dipeptides/pharmacokinetics , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Guinea Pigs , Indoles/pharmacology , Manganese/pharmacology , Meglumine/analogs & derivatives , Meglumine/pharmacology , Pentagastrin/antagonists & inhibitors , Pentagastrin/pharmacology , Rats , Receptors, Cholecystokinin/agonists , Receptors, Cholecystokinin/antagonists & inhibitors , Tumor Cells, Cultured
8.
Z Orthop Ihre Grenzgeb ; 132(2): 112-9, 1994.
Article in German | MEDLINE | ID: mdl-8209566

ABSTRACT

The purpose of the study was to determine the influence of rotation torques on superior-inferior and anterior-posterior translation in various degrees of abduction in the glenohumeral joint. 16 cadaveric shoulders were tested using a specifically designed four-degrees-of-freedom mounting apparatus and a 6-degrees-of-freedom tracking system which allowed of dynamic and static measurements by means of ultrasound (Zebris) Internal/external rotation torques and translation forces in the inferior-superior and anterior-posterior plane were applied in 0 degrees, 45 degrees, 75 degrees and 85 degrees of abduction. Shoulders were tested intact, vented, after severing of the acromion and coracoid (7 shoulders) and after subsequent division of the anterior capsule at the glenoid margin including a T-shaped incision (8 shoulders). Venting of the capsule resulted in a significant increase in ap-translation only in abduction of less than 45 degrees. Rotation torques and an abduction of more than 45 degrees effected a centering of the humeral head against translation-forces in the anterior-posterior and superior-inferior direction. The weakening of the anterior capsule by a T-shaped incision, in which circular fibers were also severed, significantly increased the anterior translation in comparison to that obtained after an incision along the glenoid margin.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Joint Capsule/physiology , Range of Motion, Articular/physiology , Shoulder Joint/physiology , Acromion/physiopathology , Adult , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Humans , Joint Instability/physiopathology , Male , Middle Aged , Shoulder Joint/diagnostic imaging , Ultrasonography
9.
J Shoulder Elbow Surg ; 3(6): 361-70, 1994 Nov.
Article in English | MEDLINE | ID: mdl-22958840

ABSTRACT

To evaluate changes in the response of capsuloligamentous restraints to translatory forces and rotation torques caused by experimental capsulorrhaphy (T-shift modification of Bankart repair), eight cadaveric shoulders were tested. Measurements were taken in intact and vented specimens, after severance of the anterior capsule at the glenoid rim (creating an artificial Bankart lesion), T-shaped incision of the anterior capsule, and refixation of the capsule (with a standard Bankart procedure) combined with tightening by T-shift. Rotation torques and translatory forces were applied in different positions of abduction with a specifically designed mounting apparatus that had four degrees of freedom. Dynamic and static measurements were performed with a tracking sysem that had six degrees of freedom. T-shift capsulorrhaphy restored the resistance of the capsuloligamentous restraints to translatory forces in all directions. This restoration was confirmed when we compared these results with data obtained from intact joints. No significant alteration of the centering mechanism resulting from rotation torques was observed, although the extent of external and internal rotation was remarkably decreased. This T-shift modification seems to produce a symmetric reduction of the volume of the capsule without significant displacement of the humeral head.

10.
Brain Res ; 577(1): 73-9, 1992 Apr 10.
Article in English | MEDLINE | ID: mdl-1325859

ABSTRACT

The present study was undertaken to localize and characterize bradykinin (BK) binding sites in 10 microns serial sections of guinea pig brain by in vitro quantitative receptor autoradiography. Specific binding of [125I-Tyr8]bradykinin ([125I]BK) was localized in the medulla oblongata to the regions of the nucleus of the solitary tract (nTS), the area postrema (AP), the dorsal motor nucleus of the vagus (X) and the caudal subnucleus of the spinal trigeminal nucleus. No significant specific [125I]BK binding was seen in other brain regions. The specific binding (85-90% of total binding) was of high affinity and saturable with a KD of 73.5 +/- 9.9 pM and a Bmax of 27.8 +/- 1.9 amol per mm2 of tissue. In competition studies, the rank order of potencies was: BK greater than Met-Lys-BK greater than Lys-BK much greater than Des-Arg9-BK. The B2 receptor antagonist D-Arg0-Hyp3-Thi5,8-D-Phe7-BK inhibited [125I]BK binding with a Ki value of 3.5 +/- 1.5 nM while Des-Arg9-[Leu8]-BK, a B1 receptor antagonist did not significantly inhibit [125I]BK binding in concentrations up to 10 microM. Our finding of specific high affinity [125I]BK binding sites in the nTS, AP and the X is important because these brain areas are known to be involved in central cardiovascular regulation. Moreover, our results suggest that the specific [125I]BK binding sites in the guinea pig medulla are of the bradykinin B2 receptor type.


Subject(s)
Bradykinin/analysis , Brain Chemistry/physiology , Receptors, Neurotransmitter/analysis , Animals , Autoradiography , Guinea Pigs , Iodine Radioisotopes , Radioligand Assay , Receptors, Bradykinin
11.
Cryobiology ; 28(3): 294-301, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1864085

ABSTRACT

This study utilized microvascular corrosion casting techniques to evaluate changes in the microvascular patency of rat hindpaws cooled to four different subzero temperatures. Left hindpaws of anesthetized rats in group 1 were cooled to -5 degrees C, in group 2 to -15 degrees C, in group 3 to heat of fusion (HOF), and in group 4 to HOF and then to -15 degrees C. Although freezing did not take place in the hindpaws of groups 1 and 2, initiation of freezing in the tissues, as indicated by HOF, did occur in groups 3 and 4. Cooled hindpaws were rapidly rewarmed. Right hindpaws served as controls. Microvascular corrosion casts were made from the left and right hindpaws of all animals. There was no significant difference when the mean cast weights of cooled hindpaws from groups 1, 2, and 3 were compared to the mean cast weights of their respective control hindpaws. In group 4, there was a significant difference (P less than 0.05) when the mean cast weight of the cooled hindpaws (47.69 +/- 9.05, mg +/- SEM) was compared to that of the control hindpaws (80.63 +/- 12.23). Since, in this acute experiment, a loss of vascular integrity occurred when the hindpaws in group 4 were cooled to -15 degrees C after reaching HOF, the initiation of freezing alone was not sufficient to reduce mean cast weight.


Subject(s)
Cold Temperature/adverse effects , Corrosion Casting , Frostbite/etiology , Microcirculation/injuries , Animals , Frostbite/pathology , Hindlimb , Male , Microcirculation/pathology , Microscopy, Electron, Scanning , Rats , Rats, Inbred Strains
12.
Cryobiology ; 26(1): 85-92, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2924596

ABSTRACT

The extent of microvascular damage from frostbite can be accurately demonstrated by vascular microcorrosion casting techniques (P. S. Daum, W. D. Bowers, Jr., J. Tejada, and M. P. Hamlet, Cryobiology 24, 65-73, 1987). In the present investigation, the peripheral vasodilator buflomedil was evaluated for its ability to ameliorate microcirculatory damage from acute experimentally induced freeze injury. This drug has been reported to decrease tissue loss in human frostbite patients when given intravenously during thawing (J. Foray, P. E. Baisse, J. P. Mont, and Cl. Cahen, Sem. Hop. Paris 56, 490-497, 1980). In seven groups of anesthetized rats, left hindpaws were cooled to heat of fusion; cooling continued until the temperature in the footpads fell to -15 degrees C. Prior to cooling, group 1 received a tail vein injection of 1 ml saline/kg, while group 2 received 10 mg buflomedil/kg. Immediately following cooling, group 3 received an injection of 10 mg buflomedil/kg. Hindpaws were rapidly rewarmed in a 40 degree C bath. During rewarming, left hindpaws from group 4 were immersed in deionized water, from group 5 in 24 mg buflomedil in deionized water, from group 6 in 30% dimethyl sulfoxide (Me2SO), and from group 7 in 24 mg buflomedil in 30% Me2SO. Right hindpaws served as controls. Vascular microcorrosion casts were made from left and right hindpaws of all groups. There was no significant difference in mean cast weights when frozen hindpaws of the seven groups were compared, although treatment with buflomedil increased the mean cast weight of control hindpaws from groups 3 and 7. It therefore appears that, in this acute model for frostbite, buflomedil does not improve vascular patency.


Subject(s)
Foot/blood supply , Frostbite/drug therapy , Pyrrolidines/therapeutic use , Vasodilator Agents/therapeutic use , Animals , Drug Evaluation , Frostbite/pathology , Hindlimb/blood supply , Male , Microscopy, Electron, Scanning , Rats , Rats, Inbred Strains
13.
Cryobiology ; 24(1): 65-73, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3816288

ABSTRACT

The use of vascular microcorrosion casts (vascular replicas) has made it possible to demonstrate the degree of damage to the microcirculation in experimentally induced frostbite. This approach provides a direct method for demonstrating vascular patency. Four groups of animals were used in this investigation. The left hind limbs of anesthetized rats were cooled to -10 degrees C in groups one and three and to -20 degrees C in groups two and four, as measured by needle thermocouples placed under the gastrocnemius muscles. Thermocouples were also placed in the left hind footpads of groups three and four. The sheathed limbs were cooled in an alcohol bath at approximately 1.1 degree C per minute. All limbs exposed to the cold bath were rewarmed to 37 degrees C in a 40 degree C water bath. The right hind limbs served as uninjured controls. The footpad temperatures recorded in groups three and four were used in conjunction with the temperatures recorded under the gastrocnemius muscles to characterize the footpad temperatures in groups one and two. Vascular microcorrosion casts were made from the left and right hind paws of groups one and two using Batson's modified methyl methacrylate. Scanning electron microscopic examination of the casts demonstrated dramatic differences between the vascular integrity of control paws and that of frozen paws. Exposure to the cold temperatures destroyed most of the microcirculation. In addition, the weights of the casts from the control paws were significantly different from the weights of the casts from the frozen paws. It was concluded that this model for evaluating frostbite injury accurately demonstrates the extent of microvascular damage and has significant potential as a method for evaluating therapeutic drug regimens.


Subject(s)
Frostbite/etiology , Microcirculation/anatomy & histology , Muscles/blood supply , Animals , Freezing , Frostbite/physiopathology , Male , Mice , Microcirculation/physiopathology , Microcirculation/ultrastructure , Microscopy, Electron, Scanning , Models, Anatomic
14.
Article in English | MEDLINE | ID: mdl-2890236

ABSTRACT

Several laboratories have demonstrated the value of the isolated perfused rat liver as a suitable model for heat-induced hepatic injury in vivo. Membrane changes caused by perfusion of rat livers at 42 degrees C for 90 min were similar to those induced by toxic chemicals or hypoxia. In an evaluation of several categories of drugs reported to reduce cell injury, calcium antagonists (nifedipine, dantrolene, and verapamil), were evaluated for their therapeutic potential for heat injury. Isolated rat livers were perfused at 42 degrees C for 90 min with and without calcium antagonists. Livers were also perfused at 37 degrees C. Potassium and transaminase leakage, bile production and ultrastructure were used to evaluate their responses. Neither of the three calcium antagonists significantly improved any of the functional parameters measured. However, dantrolene produced dilated or vesicular rough endoplasmic reticulum in the heated livers. These changes suggest selective intracellular action on endoplasmic reticulum of heated livers. Ring-shaped mitochondria and vesicular endoplasmic reticulum were observed in the heated, verapamil-treated livers, but these could not be quantitatively distinguished from controls. Nifedipine did not appear to alter intracellular membranes, but did increase bile production.


Subject(s)
Calcium Channel Blockers/pharmacology , Hyperthermia, Induced/adverse effects , Liver/drug effects , Animals , Aspartate Aminotransferases/analysis , Bile/metabolism , Dantrolene/pharmacology , In Vitro Techniques , Liver/ultrastructure , Male , Microscopy, Electron , Nifedipine/pharmacology , Perfusion , Rats , Verapamil/pharmacology
15.
Science ; 235(4787): 460-5, 1987 Jan 23.
Article in English | MEDLINE | ID: mdl-17810340

ABSTRACT

Acid deposition and photochemical smog are urban air pollution problems, and they remain localized as long as the sulfur, nitrogen, and hydrocarbon pollutants are confined to the lower troposphere (below about 1-kilometer altitude) where they are short-lived. If, however, the contaminants are rapidly transported to the upper troposphere, then their atmospheric residence times grow and their range of influence expands dramatically. Although this vertical transport ameliorates some of the effects of acid rain by diluting atmospheric acids, it exacerbates global tropospheric ozone production by redistributing the necessary nitrogen catalysts. Results of recent computer simulations suggest that thunderstorms are one means of rapid vertical transport. To test this hypothesis, several research aircraft near a midwestern thunderstrom measured carbon monoxide, hydrocarbons, ozone, and reactive nitrogen compounds. Their concentrations were much greater in the outflow region of the storm, up to 11 kilometers in altitude, than in surrounding air. Trace gas measurements can thus be used to track the motion of air in and around a cloud. Thunderstorms may transform local air pollution problems into regional or global atmospheric chemistry problems.

16.
J Neurochem ; 46(4): 1094-101, 1986 Apr.
Article in English | MEDLINE | ID: mdl-3005503

ABSTRACT

This study was directed at the issue of whether or not subpopulations of cholecystokinin (CCK) receptors exist within the CNS. This was achieved through the use of two radiolabelled probes, namely [125I] Bolton-Hunter (BH) CCK 8 and [3H]pentagastrin (Boc-beta-Ala CCK 4), in comparative studies under identical conditions. Both probes bound with high affinity to the mouse cerebral cortical CCK receptor binding site with apparent equilibrium dissociation constants (KD) of 1.9 nM and 1.4 nM for [3H]pentagastrin and [125I]BH CCK 8, respectively. The maximal binding capacity was 1.05 and 1.15 pmol/g weight for the tritium and iodinated probes, respectively. Hill analysis yielded Hill numbers close to unity, suggesting the absence of more than one binding site and the lack of cooperativity of CCK receptor binding. Kinetic studies revealed binding site homogeneity in that no evidence of multiphasic dissociation curves was seen. Computerised analysis of displacement binding data using LIGAND established that both radiolabelled probes bound to a single site, with the one-site model providing the best fit of the data. Similar rank orders of potency were obtained for various fragments of CCK 8 in competing for the CCK receptor, labelled with either probe. Both CCK 8 and CCK 4 bound with roughly equinanomolar affinity. These studies demonstrate that both CCK 8 and its shorter C-terminal fragment CCK 4 bind to a single class of high-affinity binding site, with as yet no evidence of CNS CCK receptor multiplicity.


Subject(s)
Cerebral Cortex/metabolism , Pentagastrin/metabolism , Receptors, Cell Surface/metabolism , Sincalide/analogs & derivatives , Succinimides/metabolism , Animals , Binding, Competitive , Cell Membrane/metabolism , Kinetics , Male , Mice , Receptors, Cholecystokinin , Sincalide/metabolism
17.
Lab Invest ; 51(6): 675-81, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6389976

ABSTRACT

Isolated rat livers were perfused at 37 degrees, 41 degrees, 42 degrees, and 43 degrees C with and without insulin and cortisol. Two additional groups were perfused at 42 degrees C with either hormone alone. The perfusate contained red blood cells, amino acids, and albumin in Krebs-Ringer bicarbonate. Bile flow was significantly increased by hormones at 37 degrees C. Bile flow was also increased by hormones at all other temperatures. At 41 degrees C, K+ leakage was the only parameter that indicated injury. Insulin and cortisol significantly reduced K+ leakage at this temperature compared to those without hormones. At 42 degrees C, insulin and cortisol reduced K+ leakage, increased bile flow, reduced transaminase release, and improved ultrastructural integrity. The enhanced bile flow was due primarily to insulin. A reduction in K+ leakage required both insulin and cortisol. Transaminase leakage responded to either hormone alone or in combination; however, only the cortisol-treated group showed a statistically significant reduction in transaminase leakage. At 43 degrees C, indications of irreversible injury were evident and hormones had no beneficial effects. Loss of membrane homeostasis appeared to be the initial event.


Subject(s)
Hot Temperature , Hydrocortisone/pharmacology , Insulin/pharmacology , Liver/physiology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Bile/physiology , In Vitro Techniques , Kinetics , Liver/drug effects , Liver/ultrastructure , Male , Microscopy, Electron , Perfusion , Potassium/metabolism , Rats
18.
J Neurochem ; 43(1): 25-32, 1984 Jul.
Article in English | MEDLINE | ID: mdl-6327916

ABSTRACT

Histamine stimulated the accumulation of [3H]inositol 1-phosphate in the presence of 10 mM LiCl in [3H]inositol-loaded tissue slices from several regions of guinea pig brain. The level of [3H]inositol 1-phosphate increased approximately linearly, after an initial lag period, up to a time of 120 min. In the absence of lithium ions the accumulation of the 1-phosphate stimulated by histamine in cerebral cortical and hippocampal slices was markedly reduced. Lithium ions had much less effect on the response to histamine in cerebellar slices. The characteristics of the response to histamine were consistent with mediation by H1 receptors, and the affinity constants derived for mepyramine (2.3 X 10(9) M-1) and methapyrilene (1.8 X 10(8) M-1) were similar to those reported from measurements on other H1 responses in the guinea pig. The EC50 for histamine was similar in cerebellum, cerebral cortex, hippocampus, and hypothalamus. The position of the dose-response curve for histamine in cerebral cortical slices was similar to that of the curve for the receptor binding of histamine deduced from histamine inhibition of [3H]mepyramine binding.


Subject(s)
Brain/metabolism , Histamine/pharmacology , Inositol Phosphates , Inositol/analogs & derivatives , Lithium/pharmacology , Animals , Brain/drug effects , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Guinea Pigs , Inositol/metabolism , Male , Pyrilamine/pharmacology , Receptors, Histamine H1/metabolism , Time Factors
20.
Br J Pharmacol ; 77(2): 347-57, 1982 Oct.
Article in English | MEDLINE | ID: mdl-6291688

ABSTRACT

1 A range of histamine analogues have been examined as potentiators of the adenosine-stimulated accumulation of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in slices of guinea-pig cerebral cortex. Dose-response curves were constructed for the 6 most active compounds and characterized in terms of the IC50, the slope and the maximum response attainable relative to that of histamine. 2 Histamine, 2-thiazolylethylamine and N alpha-methylhistamine produced a maximal or near maximal response. N alpha, N alpha-dimethylhistamine and 2-methylhistamine appear to be partial agonists. 3 The response to all the agonists was practically abolished by mepyramine 1 microM, indicating that the response is mediated largely or wholly via histamine H1-receptors. 4 The relative potencies of the agonists on cyclic AMP accumulation were in general similar to relative potencies in causing contraction of intestinal smooth muscle. The biggest difference was observed with N alpha-methylhistamine. 5 The histamine analogues were also examined as inhibitors of [3H]-mepyramine binding in homogenates of guinea-pig cerebral cortex. The inhibition curves were characterized in terms of IC50, the slope and the maximum percentage inhibition. This last value was compared with the inhibition produced by promethazine 2 microM. 6 For the 6 most potent agonists, the EC50 for cyclic AMP accumulation was compared with the IC50 against [3H]-mepyramine binding, corrected for inhibition of non-receptor binding and for competition with [3H]-mepyramine. With the possible exception of 2-pyridylethylamine, the values did not differ by more than a factor of 3.


Subject(s)
Adenosine/pharmacology , Brain/drug effects , Cyclic AMP/metabolism , Receptors, Histamine H1/drug effects , Receptors, Histamine/drug effects , Animals , Brain/metabolism , Female , Guinea Pigs , Histamine/analogs & derivatives , Histamine/pharmacology , In Vitro Techniques , Male , Promethazine/pharmacology , Pyrilamine/metabolism , Receptors, Histamine H2/physiology
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