A simplified cyclic adenosine monophosphate-mediated sweat rate test for quantitative measure of cystic fibrosis transmembrane regulator (CFTR) function.
OBJECTIVE
Sweat production is stimulated by both cholinergic and beta-adrenergic pathways in the sweat gland secretory coil. beta-Adrenergic pathway-mediated sweating is absent in cystic fibrosis (CF) because cyclic adenosine monophosphate (cAMP)-mediated chloride transport through the cystic fibrosis transmembrane regulator (CFTR) is disrupted. We report the development of a rapid, reproducible, macroscopic, and quantitative methodology to test the hypothesis that beta-adrenergic sweat rate discriminates among 3 different CFTR phenotypes-CF, heterozygote CF carriers, and non-CF.


METHODS
Intradermal injection of a mixture of 50 micromol/L isoproterenol, 5 mmol/L aminophylline (to potentiate the beta-adrenergic stimulation), and 140 micromol/L atropine (to block potential cholinergic stimulation) in lactated Ringer's solution was performed in duplicate on one forearm. A single injection of 0.5 mmol/L methacholine to stimulate sweat production by the cholinergic pathway was performed on the other forearm. Sweat rate was determined as the amount of sweat collected on filter paper over 20 minutes.


CONCLUSIONS
Median cAMP-mediated sweat rates were 1.45 mg/20 min (CF, n = 29), 2.55 mg/20 min (CF heterozygote carriers, n = 30), and 3.65 mg/20 min (non-CF, n = 30) and were significantly different in all 3 groups (P =.0001, Kruskal-Wallis test). Methacholine-stimulated sweat rates were similar for all 3 groups. The cAMP-mediated sweat rate test may be a useful endpoint for studies of new agents to increase the function of CFTR.
Callen
A
A
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Diener-West
M
M
Zeitlin
P L
PL
Rubenstein
R C
RC
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D002648:Child; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017354:Point Mutation / Q000235:genetics; D013542:Sweat / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; C505032:CFTR protein, human; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D016210:Methacholine Chloride; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000628:Aminophylline; D001285:Atropine; D000242:Cyclic AMP; D007545:Isoproterenol