Abstract
To explore the existence of multiplicity of &kgr; receptor in the heart, two series of experiments were performed. In the first we studied the antagonistic actions of nor-BNI, a selective &kgr;1antagonist, and quadazocine, a preferential &kgr;2antagonist, against the effects of U50488, a selective &kgr;1agonist, and bremazocine, a universal agonist preferentially binding to &kgr;2receptor, on the electrically stimulated [Ca2+]itransient and forskolin-stimulated cAMP accumulation in the rat ventricular myocyte. In the second series of experiments, we determined and compared the effects of above two &kgr; receptor agonists in the ventricular myocytes made insensitive to &kgr;1and &kgr;2agonists by prior exposure to the respective agonists. At the concentration range of 3×10-6–3×10-5m , both U50488 and bremazocine dose-dependently inhibited the [Ca2+]itransient induced by electrical stimulation. The inhibitory effects of U50488 and bremazocine were antagonized by nor-BNI and quadazocine. The antagonistic actions of nor-BNI were significantly greater against the effects of U50488, but smaller against the effects of bremazocine than those of quadazocine. At 1×10-6–5×10-5m , both U50488 and bremazocine dose-dependently and significantly inhibited the forskolin-induced cAMP accumulation. The inhibitory effect of 30 μm U50488 on cAMP accumulation was significantly attenuated by 5 μm nor-BNI, but not by quadazocine at the same concentration; whereas the effect of 30 μm bremazocine was significantly blocked by 5 μm quadazocine, but not by nor-BNI at the same concentration. The inhibitory effect of 30 μm U50488 on electrically stimulated [Ca2+]iwas abolished by preincubation of myocytes with 10-6m U50488 for 24 h, but not with 10-6m bremazocine for 24 h; whereas the inhibitory effect of 30 μm bremazocine on electrically stimulated [Ca2+]itransient was significantly attenuated after incubation of the myocyte with 10-6m bremazocine for 24 h, but not with 10-6m U50488 for 24 h. The observations indicate the existence of &kgr; receptor subtypes in the rat heart.
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