Participation of cAMP in the facilitatory action of β,γ-Methylene ATP on the noradrenaline release from rabbit ear artery

Abstract

β,γ-Methylene ATP (βγ-mATP) significantly facilitated the electrically (4 Hz) evoked release of noradrenaline (NA) from the rabbit ear artery by activation of prejunctional purinoceptors on the sympathetic nerve terminals. In the present study, we investigated whether intracellular cAMP is involved in the purinoceptor mediated facilitatory mechanisms. Forskolin, an adenylate cyclase activator, and 8-bromo cAMP, a cAMP analogue, significantly enhanced the NA-release. The enhancement of NA-release by βγ-mATP was significantly potentiated by Ro20-1724, a phosphodiesterase inhibitor, but abolished by SQ22536, an adenylate cyclase inhibitor. Both drugs alone had no effect on the NA-release. N-ethylmaleimide and pertussis toxin, inhibitors of G i-proteins, did not affect the NA-release, or the enhancement of NA-release by βγ-mATP. Alone Cholera toxin (CTX), an activator of G s-proteins, significantly increased the NA-release, but in the presence of CTX, βγ-mATP could not produce further enhancement of the NA-release. These results suggest that cAMP is closely associated with the facilitatory action of βγ-mATP on NA-release in the rabbit ear artery.