Received February 15, 2008
Revised March 12, 2008
Accepted after revision April 25, 2008
GI & Epithelial Physiology [230]
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Iontophoretic 
-adrenergic Stimulation of Human Sweat Glands: Possible Assay for CFTR Activity In Vivo
A K M Shamsuddin 1,
M M Reddy 1,
Paul M. Quinton 2*
1 University Of California San Diego
2 University of California, San Diego and University of California, Riverside
* To whom correspondence should be addressed. E-mail: pquinton{at}ucsd.edu.
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Abstract |
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With the advent of numerous candidate drugs for therapy in cystic fibrosis (CF), there is an urgent need for easily interpretable assays for testing their therapeutic value. Defects in CFTR abolished only 
-adrenergic but not cholinergic sweating in CF. Therefore, the -adrenergic response of the sweat gland may serve both as an in vivo diagnostic tool for CF as well as a quantitative assay for testing the efficacy of new drugs designed to restore CFTR function in CF. Hence, with the objective of defining optimal conditions for stimulating -adrenergic sweating, we have investigated the components and pharmacology of sweat secretion using cell cultures and intact sweat glands. We studied the electrical responses and ionic mechanisms involved in -adrenergic and cholinergic sweating. We also tested the efficacy of different -adrenergic agonists. Our results indicated that in normal subjects the cholinergic secretory response is mediated by activation of Ca2+ dependent Cl- as well as K+ conductances. In contrast the -adrenergic secretory response is mediated exclusively by activation of a cAMP dependent CFTR Cl- conductance without a concurrent activation of a K+ conductance. Thus, the electrochemical driving forces generated by -adrenergic agonists are significantly smaller as compared to those generated by cholinergic agonists, which in turn reflects in smaller -adrenergic secretory responses as compared to cholinergic secretory responses. Furthermore, the -adrenergic agonists, isoproprenaline and salbutamol, induced sweat secretion only when applied in combination with an adenylyl cyclase activator (forskolin) or a phosphodiesterase inhibitor (3-Isobutyl-1-methylxanthine, aminophylline or theophylline). We surmise that to obtain consistent -adrenergic sweat responses, levels of intracellular cAMP beyond that achievable with a -adrenergic agonist alone are essential. -adrenergic secretion can be stimulated in vivo by concurrent iontophoresis of these drugs in normal, but not in CF, subjects.
Key Words:
Adrenergic, Secretion, Sweat
