Purine- and nucleotide-mediated relaxation of rabbit thoracic aorta: common and different sites of action.
The mechanisms of the relaxant effect of purines and pyrimidines in New Zealand rabbit isolated aorta were investigated at endothelial and smooth muscle cell levels. Endothelium-mediated relaxation by ATP was only partially inhibited by the P2-purinoceptor antagonist suramin (0.1 mM). The pyrimidine UTP produced vasodilation by acting at the endothelial level and relaxation was not antagonized by suramin (0.1 mM). This effect was not mediated by P2 purinoceptors, indicating that UTP, like ATP to a certain extent, produces relaxation via an endothelium nucleotide (N) pyrimidinoceptor. ATP, ADP, AMP, adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) and inosine were all active as relaxants on smooth muscle. The NECA relaxant effect was not antagonized by P1-purinoceptor antagonists 3,7-dimethyl-1-propargylxanthine (50 microM) or 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (5 microM), excluding a P1-mediated effect. P2-related activity was excluded because adenosine-mediated relaxation was not antagonized by suramin (0.1 mM). UTP was ineffective as a relaxant at smooth muscle level, thus excluding the presence of muscular nucleotide (N) pyrimidinoceptor and suggesting a P3 purinoceptor. The rank order of potency of this muscle purinoceptor was NECA > adenosine > ATP approximately equal to ADP approximately equal to AMP approximately equal to inosine.
Chinellato
A
A
Department of Pharmacology, University of Padova, Italy.
Ragazzi
E
E
Pandolfo
L
L
Froldi
G
G
Caparrotta
L
L
Fassina
G
G
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007288:Inosine / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009711:Nucleotides / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D011817:Rabbits; D013498:Suramin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D009711:Nucleotides; D011687:Purines; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D007288:Inosine; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D014544:Uridine Triphosphate