Cross-talk with (2)-adrenoceptors enhances ligand affinity properties from endothelial alpha(1D)-adrenoceptors that mediates carotid relaxation

Autor(es)

Pernomian, Larissa ^[1] ; Gomes, Mayara Santos ^[1] ; Araujo Restini, Carolina Baraldi ^[2] ; Pupo, Andre Sampaio ^[3] ; de Oliveira, Ana Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, BR-14049 Ribeirao Preto - Brazil

^[2] Univ Ribeirao Preto, Fac Med, Ribeirao Preto - Brazil

^[3] Univ Estadual Paulista, Inst Biosci Botucatu, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacy and Pharmacology; v. 65, n. 9, p. 1337-1346, SEP 2013.
• Citações Web of Science: 14

Resumo

Objectives Our main objectives were to investigate the affinity properties of endothelial and muscular (1D)-adrenoceptors and to characterize the cross-talk between endothelial (1D)-adrenoceptors and (2)-adrenoceptors in rat carotid. Methods Relaxation and contraction concentration-response curves for phenylephrine ((1)-adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 ((1D)-adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 ((2)-adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA(2) values of BMY7378. Key Findings BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA(2) value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA(2) value similar to that obtained in phenylephrine-induced contraction. Conclusions Endothelial (1D)-adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with (2)-adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation. (AU)

• Processo FAPESP: 12/00640-7 - Estudo das consequências do processo inflamatório induzido por receptores AT1 durante aterosclerose sobre o eixo ECA2 - angiotensina-(1-7) -Mas em aorta de camundongo e da participação de receptores Mas nos efeitos vaso- e ateroprotetores de losartan
• Beneficiário: Larissa Pernomian
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado