Inhibition of noradrenaline release in the pig coronary artery via a novel serotonin receptor.
In pig coronary artery preincubated with [3H]noradrenaline, the effects of serotonin (5-HT) receptor agonists and antagonists on the electrically evoked (0.66 Hz) tritium overflow were determined. Tritium overflow was inhibited by 5-HT, 5-aminotryptamine, N,N-dimethyl-5-hydroxytryptamine, 5-hydroxytryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and tryptamine. The maximum inhibition obtainable with 5-HT was by about 35%, its pIC20 value was 7.85. 8-Hydroxy-di(n-propylamino)tetralin, urapidil, ipsapirone, 5-carboxamidotryptamine, 4-hydroxytryptamine, 5-methoxytryptamine and alpha-methyl-5-hydroxytryptamine did not decrease 3H overflow. The inhibitory effect of 5-HT was not antagonized by ketanserin, mesulergine, metitepine, propranolol, (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930) and yohimbine. Additionally, it was not altered by indomethacin. We conclude from the present data that the sympathetic nerves of the pig coronary artery are endowed with inhibitory presynaptic 5-HT receptors which do not belong to the 5-HT1, 5-HT2 or 5-HT3 receptor type but seem to represent a so far unknown receptor class.
Molderings
G J
GJ
Institute of Pharmacology and Toxicology, Rheinische Friedrich-Wilhelms-Universität Bonn, F.R.G.
Göthert
M
M
Fink
K
K
Roth
E
E
Schlicker
E
E
D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013552:Swine; D014363:Tryptamines / Q000494:pharmacology
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D009638:Norepinephrine