5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra

Eur J Pharmacol. 1988 Jul 7;151(2):189-96. doi: 10.1016/0014-2999(88)90799-6.

Abstract

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 EC50 of 67, 40, 83, 100 and 200 nM respectively. 8-Hydroxydipropylaminotetralin (8-OH-DPAT) and ipsapirone, both 5-HT1A-selective drugs, were respectively weak and ineffective to inhibit forskolin-stimulated adenylate cyclase. CGS 120 66B was almost as potent (EC50 = 100 nM) as 5-HT to inhibit the forskolin-stimulated adenylate cyclase in rat substantia nigra homogenates whereas this preferential 5-HT1B agonist was 100 times less potent than 5-HT in hippocampus guinea pig homogenates. Spiroperidol, mesulergine and ketanserin, which are potent 5-HT1A, 5-HT1C and 5-HT2 antagonists respectively, were unable to reverse the 5-HT-mediated inhibition of forskolin-stimulated adenylate cyclase whereas the beta-adrenoceptor antagonists, (+/-)-cyanopindolol and (+/-)-propranolol or metergoline, fully reversed the 5-HT effect with calculated Ki 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-HT1B binding sites. Our conclusion is that, in addition to the 5-HT1A receptor, the 5-HT1B receptor is also negatively coupled to adenylate cyclase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Colforsin / pharmacology
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Serotonin / pharmacology
  • Substantia Nigra / metabolism*
  • Tetrahydronaphthalenes / pharmacology
  • Tissue Distribution

Substances

  • Adenylyl Cyclase Inhibitors
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • Colforsin
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Adenylyl Cyclases