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A study of the H 2 ‐receptor for histamine stimulating adenylate cyclase in homogenates of guinea‐pig lung parenchyma
Author(s) -
Foreman J.C.,
Norris D.B.,
Rising T.J.,
Webber S.E.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10154.x
Subject(s) - dimaprit , histamine , cyclase , histamine h2 receptor , medicine , endocrinology , mepyramine , forskolin , adenylate kinase , cimetidine , guinea pig , chemistry , stimulation , biology , antagonist , receptor
1 The effect of forskolin and several H 2 ‐agonists was investigated on the activity of adenylate cyclase in homogenates of guinea‐pig lung parenchyma. 2 Histamine, 0.1 μM to 1 mM, dimaprit, 1 μM to 10 mM, 4‐methyl histamine, 0.1 μM to 10 mM, impromidine, 10 nM to 10μM and forskolin, 1 nM to 100 μM, all produced a dose‐dependent stimulation of adenylate cyclase activity above the basal level. 3 The histamine H 1 ‐receptor antagonist mepyramine, 10 μM, and β‐adrenoceptor antagonist propranolol, 10 μM, had no effect on the stimulation by histamine of adenylate cyclase. 4 The dose‐response curve for stimulation by histamine of adenylate cyclase was shifted to the right in a dose‐dependent manner by increasing concentrations of several H 2 ‐antagonists. Schild plots constructed for each H 2 ‐antagonist produced straight lines with slopes not significantly different from unity. The equilibrium dissociation constants obtained for the H 2 ‐antagonists in this study were similar to those previously reported for inhibition of dimaprit‐induced relaxation of the pre‐contracted lung strip, inhibition of [ 3 H]‐tiotidine binding to homogenates of guinea‐pig lung parenchyma and inhibition of histamine‐stimulated adenylate cyclase in guinea‐pig gastric mucosa.