Inhibition by 5-HT of forskolin-induced cAMP formation in the renal opossum epithelial cell line OK : mediation by a 5-HT1B like receptor and antagonism by methiothepin

• Published in: Neuropharmacology Vol. 33; no. 1; pp. 67 - 75
• Main Authors: PAUWELS, P. J, PALMIER, C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 1994
• Subjects: Adrenergic alpha-2 Receptor Antagonists; Adrenergic beta-Antagonists - pharmacology; Animals; Biological and medical sciences; Caudate Nucleus - drug effects; Caudate Nucleus - metabolism; Cell Line; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Colforsin - antagonists & inhibitors; Colforsin - pharmacology; Cyclic AMP - biosynthesis; Epithelial Cells; Epithelium - metabolism; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; In Vitro Techniques; Membranes - drug effects; Membranes - metabolism; Methiothepin - pharmacology; Opossums - metabolism; Rats; Receptors, Serotonin - drug effects; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Sheep; Vertebrates: urinary system; Cell culture; Agonist; Serotonin; Enzyme; Phosphorus-oxygen lyases; Cyclic AMP; Lyases; In vitro; Kidney; Adenylate cyclase; Urinary system; Animal; Neuromediator; Antagonist
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(94)90098-1

The functional activity of various 5-HT receptor agonists, including 5-CT, sumatriptan, CP 93, 129 and 1-naphtylpiperazine, and of drugs known to bind with high affinity to 5-HT1B (pindolol, propranolol, cyanopindolol, SDZ 21,009 and isamoltane) or 5-HT1D binding sites (yohimbine and rauwolscine) was measured at 5-HT receptors that are negatively coupled to adenylate cyclase in cultures of the renal epithelial cell line OK. 5-HT receptor-mediated inhibition of adenylate cyclase was studied by measuring inhibition of cAMP formation, induced by 100 microM forskolin. Besides 5-HT, various other compounds with affinity for 5-HT receptors behaved as agonists with the following rank order of potency: RU 24,969 > 5-CT > dihydroergotamine = 5-HT > CP 93,129 > d-LSD > 1-naphtylpiperazine > sumatriptan > TFMPP = mCPP > CGS 12066B = metergoline > methysergide. The beta-adrenergic receptor blockers cyanopindolol, SDZ 21,009, (-)-pindolol and (-)-propranolol, and the alpha 2-adrenergic blockers yohimbine and rauwolscine yielded agonist activity at nanomolar and micromolar concentrations, respectively. Isamoltane acted as a partial agonist. Methiothepin was the only compound that antagonised the OK cell 5-HT receptor-mediated inhibition of forskolin-induced cAMP formation. We conclude that the OK cell 5-HT receptor has properties consistent with a 5-HT1B receptor, although differences are apparent with regard to potencies of some compounds. Methiothepin is probably the only effective antagonist at 5-HT1B receptor sites, whereas the described putative 5-HT1B receptor antagonists have to be considered as partial agonists, yielding agonist or antagonist activity depending on the system that is studied.