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 μM), 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) > 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) > 5-hydroxytryptamine (5-HT) = 5-methoxytryptamine (5-OCH3-T) > trifluoromethylphenylpiperazine (TFMPP) > 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 μM), whereas 8-OH-DPAT, 5-CT and 2-CH3-5-HT exerted a monophasic effect. In the presence of Ca2+ (1.5 μM), low cocentrations 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. 5-HT seems to enhance Ca2+-stimulated adenylate cyclase activity in the cerebral cortex via a non-typical 5-HT receptor, and to reduce enzyme activity via the 5 HT1A receptor. © 1990.