Sweat glands are innervated by sympathetic neurons which undergo a change in transmitter phenotype from noradrenergic to cholinergic during development. As soon as the glands begin to differentiate, M3 muscarinic receptor mRNA and binding sites are detectable. Receptor expression appears in the absence of innervation and is maintained after denervation. While receptor expression is not regulated by innervation, secretory responsiveness is. Muscarinic blockade during development or in adult animals results in the loss of responsiveness and its reappearance requires several days. Cholinergic muscarinic activation is most likely to regulate one or more steps in the signalling cascade that are downstream of calcium mobilization. The anterograde regulation of sweat gland responsiveness is one facet of the reciprocal interactions are required to establish a functional synapse in this system.
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