Interaction of 5-hydroxykynurenamine, L-kynurenine and kynuramine with multiple serotonin receptors in smooth muscle.
The enzymatic formation of kynurenine derivatives from tryptophan and the regulation of this metabolic pathway by both tryptophan concentrations and plasma cortisol concentrations have raised the possibility that the kynurenine derivatives, L-kynurenine, kynuramine and 5-hydroxykynurenamine (5-OH-kynurenamine) may be important as endogenous agonists or antagonists at serotonin (5-HT) receptors in smooth muscle. In fact, 5-OH-kynurenamine was an agonist at 5-HT2 receptors in the rat jugular vein and aorta, at 5-HT3 (neuronal "M") receptors in the guinea pig ileum and at 5-HT receptors in the rat stomach fundus. Maximal contractile responses to 5-OH-kynurenamine in these three smooth muscle preparations were similar to those produced by 5-HT, although 5-OH-kynurenamine was approximately 10- to 100-fold less potent than 5-HT as a contractile agonist. Using appropriate antagonists, LY53857 as a selective antagonist at 5-HT2 receptors, ICS 205-930 as a selective antagonist at 5-HT3 receptors and 1-(1-napthyl) piperazine as a potent antagonist in the rat stomach fundus, we documented further that the contractile responses to 5-OH-kynurenamine resulted from its interaction with 5-HT receptors in these tissues. Kynuramine did not contract either the rat jugular vein, aorta or the guinea pig ileum, although a contractile response did occur in the rat stomach fundus (maximal response approximately 70% of the maximal contractile response to 5-HT). High concentrations of kynuramine (10(-4) M) produced modest inhibition and reduction in maximal responses to 5-HT in the jugular vein, aorta and guinea pig ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D006168:Guinea Pigs; D007735:Kynuramine / Q000031:analogs & derivatives / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011427:Propiophenones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*
D004873:Ergolines; D011427:Propiophenones; D011985:Receptors, Serotonin; D007737:Kynurenine; D007735:Kynuramine; C001402:5-hydroxykynuramine; C032663:LY 53857; D011224:Prazosin