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Forskolin, an activator of adenylate cyclase, and its analogs were studied on the nicotinic acetylcholine receptor-ion channel complex (AChR) of rat and frog skeletal muscles. At nanomolar concentrations, forskolin caused desensitization of the AChR located at the junctional region of innervated and the extrajunctional region of chronically denervated rat soleus muscles. The desensitization of the AChR occurred without alteration of the conducting state (channel lifetime, conductance or bursting) as shown by single channel currents. Accordingly, forskolin decreased the peak amplitude of the repetitive evoked endplate currents in frog sartorius muscles. These findings taken together with the good correlation found between the effects of forskolin and its analogs on the desensitization of the nicotinic AChR and their ability to activate adenylate cyclase suggested a possible involvement of phosphorylation of AChR via cyclic AMP on the desensitization process. ForskolinNicotinic receptor cyclic AMP Desensitization Adenylate cyclase Acetylcholine sensitivity

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Bisphenol A (BPA) is used in manufacturing plastics. Even though BPA is reported to produce reproductive and behavioral toxicity in experimental animals, the direct effect of BPA on the cardiovascular system is not known. The present study was therefore undertaken to evaluate the effect of BPA, on spontaneously beating rat right atrial preparations. In this study, in vitro isometric contractions of right atria were recorded. Cumulative concentration-response of BPA on atrial contractions was obtained in the absence or presence of antagonists. BPA (0.1-100 μ m) decreased the rate and the force of atrial contractions in a concentration-dependent manner. At 100 μ m, the decreases were >90%. The BPA-induced changes were not blocked by atropine (muscarinic receptor blocker). However, pretreatment with N-ω-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or methylene blue (a guanylyl cyclase inhibitor) blocked the BPA-induced changes in rate and force. Nitroglycerine, an NO-donor, decreased the rate and force of atrial contractions. Further, the BPA-induced changes were not due to the solvent (ethanol) used to dissolve it. The present study therefore indicates that BPA decreases the atrial contractility involving NO-dependent G-cyclase signaling mechanisms.

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