title: Bradykinin increases catecholamine release via B2 receptors.
abstract: The mechanism by which bradykinin induces catecholamine release from neural tissues was investigated in two experimental models of rat origin. The rat phaeochromocytoma cell line PC12 was used to identify the subtype of bradykinin receptors involved in the stimulation of noradrenaline secretion and to compare the effects of three different B2-antagonists. An increase of catecholamine release induced by bradykinin in vivo could be confirmed by measuring plasma levels in pithed spontaneously hypertensive rats (SHR) during electric preganglionic stimulation of the spinal cord. In this whole animal model, the effects of inhibition of both uptake and alpha 2-adrenoceptors on plasma levels of noradrenaline and adrenaline were studied as well as the potentiation of exogenous bradykinin by inhibition of angiotensin I-converting enzyme and neutral endopeptidase. The receptor subtypes involved (i.e. B1 or B2) were characterized by application either of HOE 140 or desArg9-[Leu8]-bradykinin respectively. In PC12 cells bradykinin provoked a prominent increase of noradrenaline release at low concentrations (concentration required for 50% of the maximum response 1 nM), whereas the B1-agonist desArg9-bradykinin was only effective at concentrations higher than 30 microM. The effects of both kinins could be blocked by the B2-specific antagonist HOE 890307 which, like HOE 140, exerted no agonistic effect of its own. As has been shown in other neural cells, the B2-specific antagonist [Thi5,8, D-Phe7]-bradykinin only acted as a low-affinity agonist without any antagonistic effects. In experiments where the intention was to induce B1-receptor expression either by angiotensin I-converting enzyme inhibition or lipopolysaccharide application, no alteration of the secretory response of PC12 cells to bradykinin or desArg9-bradykinin could be shown. In pithed SHR, infusion of bradykinin (up to 1200 ng/min/kg) did not enhance stimulation-dependent release of noradrenaline or adrenaline. After pretreatment of the rats with ramipril bradykinin became effective and its effects were further potentiated by the concomitant application of phosphoramidon. B2-antagonism by HOE 140 abolished the bradykinin-induced release of noradrenaline and reduced the effect on plasma adrenaline. The B1-specific antagonist desArg9-[Leu8]-bradykinin was unable to diminish the stimulatory effects of bradykinin and instead brought about an increase of plasma adrenaline levels. In conclusion, bradykinin stimulates release of catecholamines from PC12 cells, peripheral sympathetic neurons and chromaffine cells by activation of ganglionic or presynaptic B2-receptors. The adrenal medulla and PC12 cells appear to be highly susceptible not only to stimulation by bradykinin, but also to non-specific stimulatory effects of certain kinin-antagonists.
authors.affiliation: Institute of Pharmacology, Medical University of Lübeck, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dendorfer
authors.forename: W
authors.initials: W
authors.lastname: Häuser
authors.forename: D
authors.initials: D
authors.lastname: Falias
authors.forename: P
authors.initials: P
authors.lastname: Dominiak
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D004558:Electric Stimulation; D006973:Hypertension / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016716:PC12 Cells; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*
chemical_list: D065168:Bradykinin Receptor Antagonists; D002395:Catecholamines; C104573:HOE 890307; D008070:Lipopolysaccharides; D018002:Receptors, Bradykinin; C065679:icatibant; D000109:Acetylcholine; D001920:Bradykinin