Differential regulation of adrenergic receptor development by sympathetic innervation.
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.
Habecker
B A
BA
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Malec
N M
NM
Landis
S C
SC
D000109:Acetylcholine / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000648:ultrastructure*; D000367:Age Factors; D000818:Animals; D003714:Denervation; D015536:Down-Regulation / Q000502:physiology; D005528:Foot / Q000294:innervation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000235:genetics*; D015290:Second Messenger Systems / Q000502:physiology; D013545:Sweat Glands / Q000196:embryology / Q000294:innervation* / Q000648:ultrastructure
D000322:Adrenergic Agonists; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D000109:Acetylcholine