Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: involvement of serotonin receptors and alpha1-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.

Evidence for a noradrenergic innervation to α1A‐adrenoceptors in rat kidney

“…Vasoconstrictor responses to PNS were inhibited by the non-selective a,-adrenoceptor antagonist, prazosin, at a concentration, 10 nM, which is approximately 30 times its equilibrium dissociation constant for a1-adrenoceptors in rat kidney (Clarke et al, 1990;Blue et al, 1991). This result confirms previous reports that x1-adrenoceptors mediate responses to PNS in rat kidney (Charlton et al, 1984;Schwartz & Malik, 1989).…”

“…Male Sprague-Dawley (Charles River) rats (300-350 g) were anaesthetized with sodium pentobarbitone (55 mg kg-', i.p.) and the renal artery and right kidney were isolated as described previously (Charlton et al, 1984;. A cannula was placed in the mesenteric artery and advanced across the abdominal aorta into the renal artery.…”

“…Thus, the present study was conducted to identify and characterize the o,-adrenoceptor mediating vasoconstrictor responses to periarterial nerve stimulation (PNS) in the isolated perfused kidney of the rat. The rat kidney was chosen because vasoconstrictor responses to PNS are mediated by o,-adrenoceptors (Charlton et al, 1984;Schwartz & Malik, 1989). Furthermore, recent studies in rat kidney have revealed that the (XA-adrenoceptor subtype mediates vasoconstrictor responses to noradrenaline (NA) Clarke et al, 1991;Munavvar & Johns, 1991;Eltz et al, 1991;Elhawary et al, 1992), although a limited involvement of MB-adrenoceptors has not been excluded .…”

Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines

“…Although this compound had no substantial affinity to α 1 ‐adrenergic receptors [130], it exerted α 2 ‐adrenergic, rauwolscine‐sensitive pressor responses, which were clearly distinct from the other serotoninergic effects [130, 144]. However, potentiation of α 1 ‐adrenoreceptor‐mediated responses to norepinephrine was also described [139, 145]. Nevertheless, serotoninergic actions of 5‐hydroxykynuramine were of interest, because of the structural similarity to the parent indoleamine.…”

“…Both kynuramine and 5-hydroxykynuramine stimulated the release of norepinephrine from sympathetic nerve fibers, but only when micromolar levels of these molecules were used [130,137,138]. Conversely, kynuramine also acted as an a 1 -adrenergic receptor antagonist [130,136,139]. As a consequence, kynuramine was capable of either causing a decrease in blood pressure of relatively short duration or an increase explained by a cardiac, indirect sympathomimetic action resulting from norepinephrine release to enhanced heart rate [130].…”