Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava.
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 beta-adrenoceptor blocking agents) on the electrically evoked 3H overflow were determined. 1. 5-HT, 5-carboxamido-tryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969), 5-methoxytryptamine, N,N-dimethyl-5HT, 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-HT1B binding sites, but not with their affinities for 5-HT1A, 5-HT1C or 5-HT2 binding sites. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A 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-HT1B (but not 5-HT1A, 5-HT1C or 5-HT2) binding sites. Ketanserin, a 5-HT2 receptor antagonist, and spiperone, which blocks 5-HT2 and 5-HT1A but not 5-HT1B or 5-HT1C receptors, failed to antagonize the effect of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Molderings
G J
GJ
Institut für Pharmakologie und Toxikologie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Federal Republic of Germany.
Fink
K
K
Schlicker
E
E
Göthert
M
M
D000818:Animals; D001808:Blood Vessels / Q000294:innervation*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014682:Vena Cava, Inferior / Q000294:innervation
D011985:Receptors, Serotonin; D009638:Norepinephrine