Developmental expression of muscarinic cholinergic receptors and coupling to phospholipase C in rat sweat glands are independent of innervation

Abstract

During development, the innervation of rat sweat glands undergoes a striking change from noradrenergic to cholinergic function. The acquisition of secretory responsiveness by the glands is temporally correlated with the appearance of cholinergic properties. In addition, responsiveness fails to appear in the absence of innervation. To investigate the basis of the onset of functional transmission and secretory responsiveness and its possible relationship to innervation, we analyzed the development of muscarinic cholinergic receptors in sweat glands, examined their expression in the glands of adult rats sympathectomized at birth, and assayed the ability of muscarinic agonists to increase phosphoinositide (PI) turnover. Autoradiographic and in situ hybridization analysis revealed that muscarinic ligand binding sites were first detectable as glands begin to form on postnatal day 4 (P4). Between P4 and P14, receptor concentration increased in parallel with mRNA for the m3 receptor subtype. On P14, the concentration of ligand binding sites approached adult levels, although only a small proportion of glands at this age secrete in response to nerve stimulation or cholinergic agonists. When the pharmacological properties of muscarinic receptors in sweat glands of adult rats sympathectomized at birth were compared to those of normal glands, the concentration and affinity determined with [N-methyl-3H]-scopolamine and the Ki values determined with the subtype-selective muscarinic antagonists 4-DAMP, pirenzepine, and AF DX-116 were similar. In addition, the molecular subtype was unchanged as was the level of m3 message. Studies of PI turnover in response to muscarinic stimulation indicated that the receptors expressed in sweat glands isolated from sympathectomized and acutely denervated, as well as control, rats were functionally coupled to phospholipase C. The absence of sympathetic innervation therefore does not appear to influence either the development of muscarinic receptors or their coupling to PI turnover. Our results suggest that functional sympathetic cholinergic innervation plays a central role in the development and maintenance of secretory function at a step distal to signal transduction across the cell membrane.

Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of mice

“…First, patients with CF do not show significant decrease in sweat secretion because elevating of cAMP can only stimulate small amounts of sweating. Second, sweat secretion in rodent is exclusively mediated by cholinergic-induced increase in Ca 2+ but not by elevating of cAMP (Grant and Landis, 1991). Therefore, our result that topiramate could decrease sweat secretion in mice rules out the possible inhibitory effect of topiramate on CFTR.…”

Effects of Topiramate on Mouse Eccrine Sweat Gland Responsiveness to Heat Exposure

“…In the current study, we observed changes in periglandular neurotransmitter levels. Nerve innervation is necessary for cholinergic agonists to elicit a sweat response [39]. During development, sympathetic neurones innervating sweat glands undergo a neurotransmitter switch from noradrenergic to cholinergic.…”

Functional requirement of aquaporin-5 in plasma membranes of sweat glands

“…Postganglionic fibers in sweat glands release acetylcholine, and catecholamines have been shown to act directly on gland cells to trigger their final differentiation for acquisition of secretory responsiveness (31). Muscarinic agonists, like pilocarpine, mimic the ability of nerve stimulation to induce sweating (32,33), and sweating is blocked by muscarinic antagonists (34). Previous studies have suggested that multiple steps are involved in the coupling of muscarinic receptor stimulation to sweat secretion (32,35).…”

“…Muscarinic agonists, like pilocarpine, mimic the ability of nerve stimulation to induce sweating (32,33), and sweating is blocked by muscarinic antagonists (34). Previous studies have suggested that multiple steps are involved in the coupling of muscarinic receptor stimulation to sweat secretion (32,35). Similar to sweat glands, rat salivary glands have abundant apical AQP5 in serous gland cells where autonomic nerve systems are innervated (8).…”