Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava

Abstract

In the rat inferior vena cava preincubated with ³H-noradrenaline, the effects of nine serotonin (5-HT) receptor agonists and of eight antagonists (including two β-adrenoceptor blocking agents) on the electrically evoked ³H overflow were determined. 1. 5-HT, 5-carboxamidotryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969), 5-methoxytryptamine, N,Ndimethyl-5-HT, tryptamine and 5-aminotryptamine inhibited the evoked ³H overflow. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT_1B binding sites, but not with their affinities for 5-HT_1A, 5-HT_1C or 5-HT₂ binding sites. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5HT_1A receptor agonist, and ipsapirone, a partial agonist at these receptors, did not inhibit overflow. 2. Cyanopindolol facilitated the evoked ³H overflow, an effect which was abolished by propranolol. The maximum inhibition of overflow obtainable with 5-HT was diminished by cyanopindolol. 3. The concentration-response curve for 5-HT was shifted to the right by metitepine, metergoline, quipazine, 6-chloro-2-(1-piperazinyl)pyrazine (MK 212) and propranolol which, given alone, did not affect ³H overflow. The apparent pA₂ values of these antagonists tended to be correlated with their affinities for 5-HT_1B (but not 5-HT_1A, 5-HT_1c or 5-HT₂) binding sites. Ketanserin, a 5-HT₂ receptor antagonist, and spiperone, which blocks 5-HT₂ and 5-HT_1A but not 5-HT_1B or 5-HT_1C receptors, failed to antagonize the effect of 5-HT. These results suggest that the inhibitory presynaptic 5-HT receptors on the sympathetic nerve terminals of the rat vena cava appear to belong to the 5-HT_1B subtype. Cyanopindolol may act as a partial agonist at these receptors, as it does at the facilitatory prosynaptic β-adrenoceptors.