Analysis of the effect of 5-hydroxykynurenamine,, a serotonin metabolite, on isolated cerebral arteries, aortas and atria

Abstract

In helically cut strips of dog and human cerebral arteries, the addition of 5-hydroxykynurenamine (5-HK) caused dose-related contractions, and this contractile response was attenuated by methysergide and lysergic acid diethylamide (LSD). Treatment of the strips with 5-HK in concentrations higher than 2 X 10- minus 6 M shifted the dose-response curve of serotonin to the right and downward. The inhibitory effect of 5-HK was reversed only partially by repeated washings, whereas the inhibition caused by methysergide and LSD was completely reversed. The contractile response to K-+ (30 mM) was reduced only slightly even at the highest concentration of 5-HK used (5 X 10-minus 5 M). In strips of rabbit aortas, the contractile effect of serotonin was markedly attenuated by 5-HK, whereas that of norepinephrine was reduced only slightly. In isolated rabbit right atria, 5-HK produced a transient increase in the rate as did serotonin, 5-HK being approximately 1/20 as potent as serotonin. The positive effect was not influenced by methysergide but was markedly attenuated or abolished by 10-minus 6 M propranolol and 3 X 10-minus 6 M cocaine. Treatment with 5-HK (5 X 10-minus 5 M) did not modify the chronotropic response to isoproterenol. It appears that 5-HK produces vascular contractions via serotonergic receptors, inhibits specifically the contractile response of arteries and aortas to serotonin and causes a tachycardia in rabbit atria by liberating catecholamines from adrenergic nerves.