OXYMETAZOLINE INHIBITS ADENYLATE-CYCLASE BY ACTIVATION OF SEROTONIN-1 RECEPTORS IN THE OK CELL, AN ESTABLISHED RENAL EPITHELIAL-CELL LINE

  • 1 July 1988
    • journal article
    • research article
    • Vol. 34  (1) , 1-7
Abstract
The nonselective .alpha.-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by .alpha.2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomolous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the .alpha.2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of .alpha.2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating .alpha.2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205, 930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin'' for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.