Nitric oxide, cAMP and the biphasic muscarinic modulation of ACh release at the lizard neuromuscular junction.

In this study, we characterized the pharmacology and physiology of the automodulation of ACh release at the lizard neuromuscular junction (NMJ). The activation of muscarinic ACh receptors generated a biphasic modulation of synaptic transmission. Muscarine-induced activation of M3 receptors (0-12 min) decreased release, whereas M1 activation (> 12 min) enhanced release. Both phases of the biphasic effect are dependent on nitric oxide. However, cAMP acting via protein kinase A is also necessary for the M1 effect. In summary, we present a novel biphasic role for muscarine and implicate M3 receptors in the inhibition and M1 receptors in the enhancement of transmitter releaseat the cholinergic lizard NMJ.