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.