Functional crosstalk of prejunctional receptors on the modulation of noradrenaline release in mesenteric vessels: A differential study of artery and vein.
The role of angiotensin II receptors, bradykinin receptors and β-adrenoceptors in the modulation of noradrenaline release and the influence of α(2)-autoinhibition in these effects was investigated in the mesenteric artery and vein. Rings of mesenteric vessels of male Wistar rats were labelled with [(3)H]-noradrenaline and the effects of modulators on tritium overflow evoked by 100 pulses at 2Hz (marked α(2)-autoinhibition) and by 20 pulses at 50Hz or 100 pulses at 2Hz plus yohimbine (1μM; reduced α(2)-autoinhibition) were evaluated. Angiotensin II and bradykinin enhanced noradrenaline release evoked by 100 pulses at 2Hz, in a concentration-dependent manner, in both vessels. These effects were attenuated under conditions of reduced α(2)-autoinhibition. The attenuation was partially reversed by activation of adenosine A(1) receptors in both vessels and by activation of P2Y receptors in the vein. Isoprenaline and the selective β(2)-adrenoceptor agonist formoterol enhanced tritium overflow independently of α(2)-autoinhibition in the vein. In the artery, the enhancement by formoterol was only observed under reduced α(2)-autoinhibition. Pharmacological characterization of the β-adrenoceptors indicated that in the artery the effect of isoprenaline was mediated by the β(1)-subtype under marked α(2)-autoinhibition and by the β(2)-subtype under reduced α(2)-autoinhibition whereas in the vein the effect was independent of α(2)-autoinhibition. The results indicate that α(2)-autoinhibition is a key determinant of the magnitude of facilitation caused by angiotensin II and bradykinin in both types of mesenteric vessels and regulates the effects mediated by β(1)-and β(2)-adrenoceptors which co-exist in the artery.
Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, Portugal.
Carlos
C
Talaia
Manuela
M
Morato
Clara
C
Quintas
Jorge
J
Gonçalves
Glória
G
Queiroz
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D008642:Mesenteric Veins / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D000804:Angiotensin II; D001920:Bradykinin; D009638:Norepinephrine