An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney

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=4.5×10⁻⁸ mol/l), both 5-carboxamidotryptamine (IC₃₀=8×10⁻⁹ mol/l) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl) indole (RU-24969, IC₃₀=2.5×10⁻⁷ 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=4×10⁻⁹ mol/l), metergoline (IC₅₀=4×10⁻⁸ mol/l) and methysergide (IC₅₀=1.3×10⁻⁷ 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-HT_1A, 5-HT_1B or 5-HT_1C subtypes.