An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Apparent distinction from the 5-HT1A, 5-HT1B and 5-HT1C subtypes

Abstract

The present study has identified a receptor for 5-hydroxytryptamine (5-HT) which functions to inhibit the stimulus-induced release of [3H] noradrenaline following sympathetic periarterial nerve stimulation to the isolated perfused rat kidney. In addition to 5-HT (IC30 = 4.5 X 10(-8) mol/l), both 5-carboxamidotryptamine (IC30 = 8 X 10(-9) mol/l) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl) indole (RU-24969, IC30 = 2.5 X 10(-7) mol/l) acted as agonists whereas 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was inactive. The inhibitory effect of 5-HT on the electrically-evoked release of tritium was antagonized in a concentration-dependent manner by methiothepin (IC50 = 4 X 10(-9) mol/l), metergoline (IC50 = 4 X 10(-8) mol/l) and methysergide (IC50 = 1.3 X 10(-7) mol/l) but not by cyproheptadine, ketanserin, mesulergine, (-)-propranolol, (+/-)-pindolol, (+/-)-cyanopindolol, metoclopramide or phentolamine. It is concluded that the receptor to 5-HT conforms to general criteria defining 5-HT1-like receptors but at the present time the receptor site cannot be fitted to the designated 5-HT1A, 5-HT1B or 5-HT1C subtypes.