Influence of alpha2-autoreceptor stimulation on the facilitation by angiotensin II and bradykinin of noradrenaline release.
The interaction between alpha(2)-autoreceptors and receptors for angiotensin II and bradykinin was studied in the heart of newborn rats. The tissues were labeled with [3H] noradrenaline and then superfused with cocaine-containing medium and stimulated electrically. Angiotensin II (30-1,000 nM) and bradykinin (10-300 nM) enhanced the evoked overflow of tritium, the maximum increase reaching 52.2 and 72.8%, respectively. In the presence of the selective alpha(2)-adrenoceptor agonist UK-14,304, the maximal effect caused by angiotensin II and bradykinin was enhanced reaching 92.1 and 87.1% for angiotensin II and bradykinin, respectively. On the contrary, in the presence of chelerythrine (a protein kinase C blocker), not only the increment in facilitation by UK-14,304, but to some extent also the basal facilitation caused by angiotensin II and bradykinin were markedly reduced (to 17.3 and 43.2%, respectively). We conclude that: 1. The stimulation of alpha2-autoreceptors enhances the facilitatory responses caused by angiotensin II and bradykinin, confirming that an ongoing alpha2-autoinhibition is required for the facilitatory influence of the peptides. 2. Protein kinase C is involved in the enhancement by angiotensin II and bradykinin of electrically-evoked release of noradrenaline from the nerve terminals.
Mota
Alberto
A
Instituto de Farmacologia e Terapêutica, Faculdade de Medicina do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal. avmota@yahoo.com
Guimarães
Serafim
S
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000470:Alkaloids; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017660:Autoreceptors / Q000819:agonists*; D053119:Benzophenanthridines; D001920:Bradykinin / Q000494:pharmacology*; D000068438:Brimonidine Tartrate; D004357:Drug Synergism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000470:Alkaloids; D017660:Autoreceptors; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D011810:Quinoxalines; D000804:Angiotensin II; D000068438:Brimonidine Tartrate; C016299:chelerythrine; D011493:Protein Kinase C; D001920:Bradykinin; D009638:Norepinephrine