5-Hydroxytryptamine receptor agonists influence calcium-stimulated adenylate cyclase activity in the cerebral cortex and hippocampus of the rat.
The effects of 5-hydroxytryptamine (5-HT) receptor agonists on calcium (Ca2+)-stimulated adenylate cyclase activity in the hippocampus and cerebral cortex of the rat were studied. In the presence of Ca2+ (1.5 microM), 5-HT dose dependently inhibited adenylate cyclase activity (EC50 = 10 +/- 2 nM). The inhibitory effect of 5-HT on Ca2(+)-stimulated adenylate cyclase was antagonized by spiperone (KB = 2 +/- 0.8 nM). The rank order of potency of 5-HT agonists to inhibit Ca2(+)-stimulated adenylate cyclase in the hippocampus was: 5-carboxamidotryptamine (5-CT) greater than 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 5-hydroxytryptamine (5-HT) = 5-methoxytryptamine (5-OCH3-T) greater than trifluoromethylphenylpiperazine (TFMPP) greater than m-chlorophenylpiperazine (mCPP). 2-Methyl-5-hydroxytryptamine (2-CH3-5-HT) did not exert an effect on Ca2(+)-stimulated enzyme activity. In the cerebral cortex 5-HT exerted a biphasic stimulatory effect on adenylate cyclase activity in the absence of Ca2+ (EC50 = 0.2 +/- 0.04 nM and 10 +/- 3 microM), whereas 8-OH-DPAT, 5-CT and 2-CH3-5-HT exerted a monophasic effect. In the presence of Ca2+ (1.5 microM), low concentrations of 5-HT, 8-OH-DPAT, 5-CT and 2-CH3-5-HT potentiated adenylate cyclase activity, whereas higher concentrations, except 2-CH3-5-HT, inhibited the enzyme activity. We propose that the 5-HT receptor mediating inhibition of Ca2(+)-stimulated adenylate cyclase in the rat hippocampus corresponds to the 5-HT1A subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
Mørk
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Department of Pharmacology, University of Copenhagen, Denmark.
Geisler
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases; D002118:Calcium