Journal of Neuroscience, Vol 16, 229-237, Copyright © 1996 by Society for Neuroscience
Differential regulation of adrenergic receptor development by sympathetic innervation
BA Habecker, NM Malec and SC Landis
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Rat sweat glands provide an interesting model system for a developmental
study of adrenergic receptor expression because their sympathetic
innervation undergoes a switch from a nonadrenergic to cholinergic and
peptidergic phenotype. alpha 1B, alpha 2B, and beta 2 receptors are
expressed in rat footpads; alpha 1 and beta 2 receptors are localized
specifically to sweat glands, and alpha 2 receptors also are expressed in
other tissues. alpha 1 and, to a lesser extent, beta 2 receptors decrease
during development, whereas alpha 2 levels remain relatively constant.
Decreased receptor expression is accompanied by the loss of alpha
1-stimulated inositol phosphate accumulation, but no change in
beta-stimulated cAMP production. The number of alpha 1 and beta 2 receptors
decreases after P21, when the sympathetic innervation no longer produces
catecholamines. Neonatal sympathectomy causes a partial failure of alpha 1
downregulation, but has no effect on beta 2 or alpha 2 receptor levels.
Therefore, at least two distinct mechanisms regulate development of
adrenergic receptors in sweat glands. Innervation-independent processes
control developmental expression of alpha 1, beta 2, and alpha 2 receptors,
and an additional, innervation- dependent mechanism influences expression
of alpha 1 receptors. Denervation at postnatal day 20, when the sympathetic
innervation is cholinergic and peptidergic, results in retention of alpha 1
receptors, but cholinergic blockade begun at P20 does not. These results
indicate that regulation of receptor expression in sweat glands is complex,
and suggest that the innervation-dependent factors that decrease alpha 1
levels during development act through a nonadrenergic, noncholinergic
mechanism.
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