Pharmacologic responsiveness of isolated single eccrine sweat glands

Abstract

Pharmacologic responsiveness of the eccrine sweat gland has never been studied under well-defined in vitro experimental conditions. Using isolated cannulated single monkey palm eccrine sweat glands, the dose response to both cholinergic and alpha- and beta-adrenergic agents and the effects of various antagonists on agonists were studied. The maximal sweat rate was highest after stimulation with cholinergic agonists, was lower with the beta-adrenergic agonist, and was least with the alpha-adrenergic agonist. Each secretory response was inhibited by its specific antagonist. Attempts to demonstrate the spare receptor, if any, by means of preincubation of the glands with N-(2-chlorethyl)dibenzylamine (Dibenamine) were unsuccessful. From the hyperbolic dose-response curves the values for KA and KB, dissociation constants for agonists and antagonists, respectively, were thus tentatively estimated according to Clark's classical receptor theory. Schild plots for each agonist-antagonist interaction produced straight lines with slopes of near unity, indicating the adequacy of the methodology. It was concluded that the isolated eccrine sweat glands retain their pharmacologic viability in vitro and show responsiveness to cholinergic as well as both alpha- and beta-adrenergic stimulations.

Abolished InsP3R2 function inhibits sweat secretion in both humans and mice

“…The secretory portion consists of 3 functionally distinct cell types: granulated (dark) cells, parietal (clear) cells, and myoepithelial cells (6,7). Upon initial stimulation of clear cells of the sweat gland by acetylcholine, intracellular [Ca 2+ ] increases and initiates a stepwise process leading to net loss of Na + , Cl -, and water into the glandular lumen (8).…”

Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro.

“…In contrast, the function of the secretory portion itself has been assumed to be normal in CF. Recent data from the authors' laboratory indicates that the isolated cannulated monkey palm eccrine sweat gland is controlled by alpha and beta adrenergic as well as cholinergic stimulation (5). Further, the role of Ca in the intracellular processes during cholinergic sweating and that of intracellular cyclic AMP (cAMP) in the beta adrenergic mechanism of sweating have been suggested (6,7).…”

“…The direct infusion of lidocaine into the excised skin was avoided. The biopsy skin was blotted of blood, sliced freehand with a razor blade, and washed in several changes of chilled Krebs-Ringer bicarbonate (KRB) solution containing (in mM): 1 5 NaCl,10 Na-acetate, 5 KCI, 1.2 MgCl2, 25 NaHCO3, 1.2 NaH2PO4, 5 glucose, and 10 mg/100 ml fatty acid-free human serum albumin (Sigma Chemical Co., St. Louis, MO). The pH of this medium was 7.45 when equilibrated with 5% C02:95% 02.…”

“…The open end of the duct near the junction of the proximal and the distal duct was held by suction in a siliconized constriction pipette as described previously (5). In some sweat glands, sweat was collected directly from the end of the secretory coil held in a pipette, as shown in Fig.…”

“…ISO or EP was then added to the bath at different concentrations with or without 10-' M (or in some glands 10-2 M) TH. Collection of sweat in an oil-filled sampling pipette and calibration of sweat volume are essentially the same as described previously (5).…”