Résumé
We measured the inhibition of forskolin-stimulated adenylate cyclase by 5-hydroxytryptamine (5-HT) and other serotonin agonists in rat substantia nigra homogenates. 5-HT, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)indole (RU 24969), 5-carboxamidotryptamine (5-CT), 1-(m-trifluoromethyl-phenyl)piperazine (TFMPP) and tryptamine inhibited forskolin-stimulated adenylate cyclase with EC
50 of 67, 40, 83, 100 and 200 nM respectively. 8-Hydroxydipropylaminotetralin (8-OH-DPAT) and ipsapirone, both 5-HT
1A-selective drugs, were respectively weak and ineffective to inhibit forskolin-stimulated adenylate cyclase. CGS 120 66B was almost as potent (EC
50 = 100 nM) as 5-HT to inhibit the forskolin-stimulated adenylate cyclase in rat substantia nigra homogenates whereas this preferential 5-HT
1B agonist was 100 times less potent than 5-HT in hippocampus guinea pig homogenates. Spiroperidol, mesulergine and ketanserin, which are potent 5-HT
1A, 5-HT
2 antagonists respectively, were unable to reverse the 5-HT-mediated inhibition of forskolin-stimulated adenylate cyclase whereas the ß-adrenoceptor antagonists, (±cyanopindolol) and (±)-propanolol or metergoline, fully reversed the 5-HT effectwith calculated K
i of 34±18, 82±19 and 248±47 nM, respectively. The pharmacological profile of the 5-HT receptor mediating the inhibition of adenylate cyclase in substantia nigra indicates that this receptor probably corresponds to 5-HT
1B binding sites. Our conclusion is that, in addition to the 5-HT
1A receptor, the 5-HT
1B receptor is also negatively coupled to adenylate cyclase.