Development and properties of the secretory response in rat sweat glands: Relationship to the induction of cholinergic function in sweat gland innervation

Abstract

Previous studies suggest that the sympathetic innervation of the sweat glands in the rat is initially noradrenergic and during development undergoes a transition in neurotransmitter phenotype to become cholinergic. To characterize this system and its development further, we have examined the adrenergic and cholinergic components of the secretory response in adult and immature rats and have studied the onset of sweating in the plantar sweat glands of developing rats. Stimulation of the sciatic nerve in adult rats elicited a secretory response which was completely blocked by the cholinergic antagonist, atropine, and was unaffected by adrenergic antagonists, indicating that nerve-evoked secretion was cholinergic. In adult rats, the sweat glands were quite sensitive to cholinergic agonists. In addition to acetylcholine, the mature sweat gland innervation contains vasoactive intestinal peptide (VIP). In some rats, the injection of VIP alone elicited a secretory response which was blocked by atropine, suggesting that the response to VIP was mediated cholinergically. In contrast to cholinergic agonists, the glands responded relatively infrequently and with reduced volumes of sweat to the α- and β-adrenergic agonists 6-fluoronorepinephrine and isoproterenol. However, when VIP, which is a potent vasodilator, was simultaneously injected with adrenergic agonists, glands in many of the injected footpads exhibited a secretory response. The response to adrenergic agonists in combination with VIP was reduced by atropine and by phentolamine plus propranolo, but was blocked completely only by a combination of the three antagonists, indicating that both adrenergic and cholinergic mechanisms were involved. In immature rats, sweating evoked by nerve stimulation first appeared at 14 days of age in 25% of the rats tested. Both the percentage of rats sweating and the number of active glands increased rapidly. At 16 days, 50% of the rats tested exhibited some active glands, and by 21 days all rats tested exhibited a secretory response. In 16-day-old rats, nerve-evoked sweating was almost completely inhibited by local injection of 1 μ M atropine, but was unaffected by phentolamine and propranolol in concentrations up to 10 μ M. Similarly, the glands were sensitive to 10 μ M muscarine, but they exhibited no secretory response to the α-adrenergic agonists, clonidine and 6-fluoronorepinephrine, nor to the β-adrenergic agonist, isoproterenol, at concentrations up to 50 μ M. The simultaneous injection of VIP with adrenergic agonists did not reveal an adrenergically mediated secretory response in 16-day-old animals. Thus, in immature as well as adult rats, the neurally evoked secretory process was mediated through a muscarinic cholinergic mechanism. The onset of nerve- and agonist-induced sweating in developing rats lagged behind the development of other cholinergic properties in the sweat glands, raising the possibility that the cholinergic responsiveness of the gland cells is induced by the release of acetylcholine from the gland innervation. Consistent with this hypothesis is the observation reported here that in adult animals in which the glands were sympathetically denervated at birth, the glands did not respond to either sciatic nerve stimulation or cholinergic agonists.