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CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE FORMATION IN GUINEA‐PIG BRAIN SLICES: EFFECT OF H 1 ‐ AND H 2 ‐HISTAMINERGIC AGONISTS
Author(s) -
Dismukes K.,
Rogers M.,
Daly J. W.
Publication year - 1976
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1976.tb04451.x-i1
Subject(s) - adenosine , histaminergic , chemistry , agonist , medicine , metiamide , histamine , endocrinology , hippocampal formation , adenosine a1 receptor , guinea pig , antagonist , adenosine receptor , receptor , biochemistry , biology , histamine h2 receptor
—A variety of histamine analogs elicit accumulations of radioactive cyclic AMP in guinea‐pig neocortical and hippocampal slices labelled during a prior incubation with [ 14 C]adenine. The H 1 agonist, 2‐aminoethylthiazole, elicits accumulation of cyclic AMP in neocortical and hippocampal slices both in the absence or presence of adenosine. The presence of adenosine increases the maximum response to 2‐aminoethylthiazole and decreases the EC 50 by nearly 10‐fold. In the absence of adenosine the effects of 2‐aminoethylthiazole are antagonized in hippocampal slices by both d ‐brompheniramine and metiamide, while in the presence of adenosine only d ‐brompheniramine is an effective antagonist. The H 2 ‐agonist, 4‐methylhistamine, elicits a somewhat smaller accumulation of cyclic AMP than does 2‐aminoethylthiazole in both cortical and hippocampal slices. In the presence of adenosine the response to 4‐methylhistamine is enhanced, but is markedly lower than that seen with the combination of adenosine and 2‐aminoethylthiazole. The dose‐response relationship for 4‐methylhistamine in the presence of adenosine appears in hippocampal slices to consist of two components. The response to 4‐methylhistamine in the absence of adenosine is blocked by metiamide, while in the presence of adenosine the response is partially blocked by both H 1 and H 2 ‐antagonists. The accumulation of cyclic AMP elicited by histamine is greatly increased by adenosine but the EC 50 is not significantly decreased. The results suggest that (i) both H 1 ‐ and H 2 ‐receptors regulate cyclic AMP‐formation in the central nervous system, (ii) the synergism between adenosine and histamine is mediated primarily by interaction with H 1 ‐receptors and (iii) that adenosine greatly increases the affinity of the H 1 ‐receptors for both H 1 and H 2 ‐agonists without affecting its affinity for histamine.