title: Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: involvement of serotonin receptors and alpha 1-adrenoceptors.
abstract: Kynuramines are endogenously occurring diamines derived from tryptophan. In the present study, we have compared the pharmacological actions of 5-hydroxykynuramine (5-OH-K) with kynuramine and 5-hydroxytryptamine (5-HT) on vascular resistance changes and responsiveness to adrenergic stimuli in the isolated perfused rat kidney. 5-OH-K was found to mimic the actions of 5-HT in that it produced vasoconstriction, potentiation of alpha 1-adrenoceptor-mediated responses to norepinephrine (NE) and periarterial nerve stimulation, and displaced specific [3H]spiroperidol binding from rat cortical membranes. With regard to all parameters measured, 5-OH-K was about 15-times less active than 5-HT. Vascular responses to 5-OH-K and 5-HT were inhibited noncompetitively by ketanserin and cyproheptadine. Unlike 5-OH-K, kynuramine, failed to evoke vasoconstriction and inhibited vascular responses to NE via alpha 1-adrenoceptors. Thus, kynuramine lacks serotonin receptor agonist activity but possesses alpha 1-adrenoceptor blocking properties. In contrast, 5-OH-K potentiates NE and acts as a serotonin agonist. The present results raise the possibility that kynuramine and 5-OH-K might act as endogenous modulators of serotonergic and adrenergic mechanisms in the renal vascular bed.
mesh_terms: D000818:Animals; D004357:Drug Synergism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D007700:Kinetics; D007735:Kynuramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D011427:Propiophenones; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D007735:Kynuramine; C001402:5-hydroxykynuramine; D009638:Norepinephrine