Fig. 9.

Schematic illustrating the physiological implications of the results of this experiment. Under normal conditions (top), ACh and SP are coexpressed in the terminal of motor neurons of the myenteric plexus and, upon stimulation of the neuron, are released by vesicular-mediated mechanisms. SP, via the NK1 receptor and as yet unknown downstream pathways, is necessary for the ability of acetylcholine (endogenous or exogenous) to phosphorylate MLC₂₀ and initiate contraction. In the presence of botulinum toxin, the release of both neurotransmitters from neurons is prevented (middle). In the absence of SP, the muscle loses its responsiveness to exogenous acetylcholine as well and fails to active MLC₂₀ and initiate contraction. These effects can be mimicked by blocking the NK1 receptor as well, suggesting that some tonic release of SP is necessary to maintain cholinergic responsiveness of smooth muscle under physiological conditions (bottom).