The eccrine sweat glands represent one of the largest cutaneous organs and serve several vital functions. Eccrine sweating is the only means by which human and some primates regulate body temperature during exercise and heat exposure. They also serve as an excretory organ as well as a device for conservation of vital electrolytes by ductal absorption. Their regulatory role in maintenance of normal physiology of the skin has been increasingly recognized. Most important, they are the target organ in the pathogenesis of cystic fibrosis and have proven to be a feasible research model the study of its basic defect. Our goal is to more completely delineate the normal mechanism of sweat secretion at the cellular or membrane level. Recognizing the mission of our laboratory as the world's most active research center studying the mechanism of sweat secretion, our goals are ambitious and comprehensive. Our specific goals include: 1) To completely elucidate all three processes of stimulus secretion coupling for eccrine sweat secretion, namely: (a) explore the possible involvement of a variety of agonists other than adrenergic and cholinergic agents and their regulatory roles; (b) signal transduction, especially the interrelationship between polyphosophoinositides metabolism, Ca2+, cyclic nucleotides and protein kinase C; and (c) mechanism of ion transport. 2) To further clarify the mechanism whereby sweat gland function improves during acclimatization. 3) To elucidate the role of proteolytic enzymes in eccrine sweating as well as in pathophysiology of the skin. 4) To clarify the role of arachidonate metabolsim in regulation of eccrine sweating. 5) To further clarify the origin and nature of major protein components in human sweat. 6) To explore the possibility of organ culture and cell culture as the future research models. Monkey palm eccrine sweat glands will be mainly used as a model. All the methodologies are currently operational in the PI's laboratory, including sweat induction from an isolated eccrine sweat gland in vitro, electrophysiological techniques, TLC, HPLC, organ and cell cultures, electron probe X-ray microanalysis, chromatographic and electrophoretic techniques.