Abstract
On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle.
Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery.
In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations.
Similar content being viewed by others
References
A.S.F. Ash andH.O. Schild,Receptors Mediating Some Actions of Histamine, Br. J. Pharmac. Chemother.27, 427–439 (1966).
J. Bareicha andM. Rocha e Silva,Occurrence of H 2 -Receptors for Histamine in the Guinea-Pig Intestine, Biochem. Pharmac.24, 1215–1219 (1975).
W. Lorenz, M. Thermann, H. Hamelmann, A. Schmal, D. Maroske, H.J. Reimann, J. Kusche, F. Schingale, P. Dormann andP. Keck,Influence of H 1 - and H 2 -Receptor Antagonists on the Effects of Histamine in the Circulatory System and on Plasma Histamine Levels, in:International Symposium on Histamine H 2 -Receptor Antagonists (Eds. C.J. Wood and M.A. Simkins; Smith, Kline and French Laboratories, Welwyn Garden City, Deltakos (U.K.) Ltd., London, 1973).
M. Thermann, W. Lorenz, A. Schmal, F. Schingale, P. Dormann andH. Hamelmann,Alterations in the Circulatory System of Anaesthesized Dogs Following Administration of Histamine and Histamine H 1 - and 2 -Receptor Antagonists in Relation to Plasma Histamine Levels, Agents and Actions5, 450–454 (1975).
N. Chand andP. Eyre,Classification and Biological Distribution of Histamine Receptor Subtypes, Agents and Actions5, 277–295 (1975).
P. Goadby andE.A. Phillips,Some Effects of Burimamide on the Isolated Perfused Pulmonary Circulation of the Guinea Pig, Br. J. Pharmac.49, 368–369 (1973).
Z.S. Ercan andR.K. Türker,Histamine Receptors in the Cat Mesenteric Circulation, Experientia32, 89–90 (1976).
Z.S. Ercan andR.K. Türker,Histamine Receptors in the Isolated Rat Stomach Fundus and Rabbit Aortic Strips, Pharmacology15, 118–126 (1977).
J. Klein andG.S. Levey,Activation of Myocardial Adenyl Cyclase by Histamine in Guinea-pig, Cat and Human Heart, J. Clin. Invest.50, 1012–1015 (1971).
R. Andersson,Role of Cyclic AMP and Ca 2+ in Mechanical and Metabolic Events in Isometrically Contracting Vascular Smooth Muscle, Acta Physiol. Scand.87, 84–95 (1973).
J.W. Daly,The Nature of Receptors Regulating the Formation of Cyclic AMP in Brain Tissue, Life Sciences18, 1349–1358 (1976).
G. Pöch, W.R. Kukovetz andN. Scholz,Specific Inhibition by Burimamide of Histamine Effects on Myocardial Contraction and Cyclic AMP, Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.280, 223–228 (1973).
H.O. Karppanen andE. Westermann,Increased Production of Cyclic AMP in Gastric Tissue by Stimulation of Histamine (H 2 )-Receptors, Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.49, 715–717 (1971).
S.R. Nahorski, K.J. Rogers andB.M. Smith,Stimulation of Cyclic Adenosine 3′, 5′-Monophosphate in Chick Cerebral Hemisphere Slices: Effects of H 1 -and H 2 -Histaminergic Agonists and Antagonists, Brain Res.126, 387–390 (1977).
D. Reinhardt, U. Schmidt, O.-E. Brodde andH.J. Schümann,H 1 - and H 2 -Receptor Mediated Responses to Histamine on Contractility and Cyclic AMP of Atrial and Papillary Muscles from Guinea-Pig Hearts, Agents and Actions7, 1–12 (1977).
S.C. Verma andJ.H. McNeill,Cardiac Histamine Receptors: Differences Between Left and Right Atria and Right Ventricle, J. Pharmac. exp. Ther.200, 352–362 (1977).
J.M. van Rossum,Cumulative Dose-Response Curves. II. Technique for the Making of Dose-Response Curves in Isolated Organs and the Evaluation of Drug Parameters, Arch. int. Pharmacodyn. Ther.143, 299–330 (1963).
A.G. Gilman,A Protein Binding Assay for Adenosine 3′,5′-Cyclic Monophosphate, Proc. nat. Acad. Sci. (Wash.)67, 305–312 (1970).
U. Schwabe andR. Ebert,Different Effects of Lipolytic Hormones and Phosphodiesterase Inhibitors on Cyclic 3′,5′-AMP Levels in Isolated Fat Cells. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.274, 287–298 (1972).
J.W. Black, W.A.M. Duncan, C.J. Durant, C.R. Ganellin andM.E. Parsons,Definition and Antagonism of Histamine H 2 -Receptors, Nature236, 385–390 (1972).
J.W. Black, W.A.M. Duncan, C.R. Ganellin, T. Hesselbo, M.E. Parsons andJ.W. Wyllie,Metiamide — an Orally Active Histamine H 2 -Receptor Antagonist, Agents and Actions3, 133–137 (1973).
J.W. Black, D.A.A. Owen andM.E. Parsons,An Analysis of the Depressor Responses to Histamine in the Cat and Dog: Involvement of Both H 1 - and H 2 -Receptors, Br. J. Pharmac.54, 319–324 (1975).
M. Albinus andK.F. Sewing,Cardiovascular Effects of Burimamide and Metiamide, Agents and Actions4, 222–226 (1974).
M.E. Parsons andD.A.A. Owen,Receptors involved in the Cardiovascular Responses to Histamine, in:International Symposium on Histamine H 2 -Receptor Antagonists (Eds. J.C. Wood and M.A. Simkins; Smith, Kline and French Laboratories, 1973), pp. 127–135.
N.K. Dutta,Some Pharmacological Properties Common to Anti-histamine Compounds. Br. Pharmac. Chemother.4, 281–289 (1949).
R. Andersson,Relationship Between Cyclic AMP, Phosphodiesterase Activity, Calcium and Contraction in Intestinal Smooth Muscle, Acta Physiol. Scand.87, 348–358 (1973).
M.L. Cohen andB.A. Berkowitz,Age-Related Changes in Vascular Responsiveness to Cyclic Nucleotides and Contractile Agonists, J. Pharmac. exp. Ther.191, 147–155 (1974).
J.H. McNeill andS.C. Verma,Blockade of Cardiac Histamine Receptors by Promethazine, Canad. J. Physiol. Pharmacol.52, 23–27 (1974).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reinhardt, D., Ritter, E., Butzheinen, R. et al. Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery. Agents and Actions 9, 155–162 (1979). https://doi.org/10.1007/BF02024727
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02024727