Lack of interaction between alpha(2)-autoreceptors and prejunctional receptors mediating a facilitatory effect on noradrenaline release.
The present study was undertaken to investigate the effect of alpha(2)-autoreceptor blockade on the facilitatory influence exerted by activation of beta -, A(2A)-adenosine- and angiotensin II receptors. Segments of a rat-tail artery, previously incubated with(3)H-noradrenaline, were subjected to electrical stimulation. The influence of isoprenaline, the compound CGS21680 and angiotensin II on the overflow of tritium evoked by electrical stimulation was checked before and after alpha(2)-adrenoceptor blockade. All the agonists used caused concentration-dependent increases of tritium overflow, the maximal effect representing increases of 44.2, 27.4 and 41.2% for isoprenaline, CGS21680 and angiotensin II, respectively. In the presence of alpha(2)-adrenoceptor blockade by phenoxybenzamine ( 1 microm) or yohimbine (33 or 100 nm), the facilitatory influence of isoprenaline, CGS21680 and angiotensin II was not significantly changed. Since this facilitatory influence, which involves the activation of G(s)- or G(q)-proteins, was not enhanced by alpha(2)-adrenoceptor blockade, it is concluded that the enhancement of the negative modulation resulting from activation of A(1)-adenosine-, muscarine- and kappa -receptors, as previously shown, should be due to the fact that the involved systems share signal transduction mechanisms, or at least G-proteins.
Mota
A
A
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, 4200-319, Portugal.
Paiva
M Q
MQ
Moura
D
D
Guimarães
S
S
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D010627:Phenethylamines; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D018047:Receptors, Purinergic P1; D046948:Secologanin Tryptamine Alkaloids; D010643:Phenoxybenzamine; D000804:Angiotensin II; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins; D000241:Adenosine; D007545:Isoproterenol