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Characterization of histamine receptors mediating the stimulation of cyclic AMP accumulation in rabbit cerebral cortical slices
Author(s) -
AlGadi M.,
Hill S.J.
Publication year - 1985
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.1476-5381.1985.tb11087.x
Subject(s) - mepyramine , histamine , metiamide , histamine h2 receptor , chemistry , histamine h1 receptor , medicine , endocrinology , agonist , dimaprit , histamine receptor , histamine h3 receptor , cimetidine , pharmacology , biology , receptor , antagonist , biochemistry
1 The characteristics of histamine‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation in slices of rabbit cerebral cortex have been investigated. 2 The selective H 2 ‐receptor antagonists, cimetidine, tiotidine, metiamide and ranitidine appeared to antagonize the stimulation of cyclic AMP accumulation elicited by histamine in a competitive manner consistent with an interaction with histamine H 2 ‐receptors. 3 The H 1 ‐preceptor antagonist mepyramine (0.8 μM) produced only a weak inhibition of the response to histamine. The inhibition appeared to be non‐competitive producing a decrease in the maximal response with little effect on the EC 50 value. 4 The specific H 2 ‐receptor agonist, impromidine, produced a maximum response of only 31 ± 2% of that obtained with histamine. Studies with histamine and impromidine in combination indicated that impromidine was not acting as a partial agonist. 2‐Thiazolylethylamine, a selective H 1 ‐agonist, produced only a weak response (EC 50 ∼ lmM) yielding a relative potency with respect to histamine (= 100) of 2.5. 5 In the presence of a supramaximal concentration of impromidine, histamine and 2‐thiazolylethylamine further elevated the response to impromidine. In these conditions the relative potency of 2‐thiazolylethylamine was increased to 59 (histamine = 100), a value which was comparable with that reported for H 1 ‐receptor‐mediated contractions of guinea‐pig ileum. 6 The H 1 ‐receptor antagonists mepyramine, promethazine, triprolidine and chlorpheniramine competitively antagonized the potentiation of impromidine‐stimulated cyclic AMP accumulation elicited by histamine and 2‐thiazolylethylamine in rabbit cerebral cortex without affecting the response to impromidine alone. (+)‐Chlorpheniramine was some 150 fold more potent than the (—)‐isomer in this respect. 7 Histamine and adenosine in combination had a much greater than additive effect on the accumulation of cyclic AMP in rabbit cerebral cortical slices. The potentiation of the adenosine response could be partially but not completely antagonized by either cimetidine or mepyramine. 8 In the presence of H 2 ‐receptor blockade with 0.02 mM tiotidine, histamine elicited a significant potentiation (EC 50 44 μM) of the response to adenosine. This response was antagonized competitively by mepyramine yielding a K B value of 0.05 μM similar to that obtained from inhibition of the potentiation of impromidine‐stimulated accumulation of cyclic AMP (0.02 μM). 9 These results suggest that there are two components in the response to histamine in rabbit cerebral cortical slices. The first component appears to be mediated by histamine H 2 ‐receptors while the second, mepyramine‐sensitive, component has some of the characteristics of an H 1 ‐receptor mediated response and requires prior stimulation of adenosine‐ or H 2 ‐receptors to produce its effect.