A simplified cyclic adenosine monophosphate-mediated sweat rate test for quantitative measure of cystic fibrosis transmembrane regulator (CFTR) function

Amy Callen, Marie Diener-West, Pamela L. Zeitlin, Ronald C. Rubenstein

Research output: Contribution to journalArticle

Abstract

Objective: Sweat production is stimulated by both cholinergic and β-adrenergic pathways in the sweat gland secretory coil. β-Adrenergic pathwav-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 β-adrenergic sweat rate discriminates among 3 different CFTR phenotypes - CE heterozygote CF carriers, and non-CF. Study design: Intradermal injection of a mixture of 50 μmol/L isoproterenol, 5 mmol/L aminophylline (to potentiate the β-adrenergic stimulation), and 140 μmol/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. Results and 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-CE 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.

Original languageEnglish (US)
Pages (from-to)849-855
Number of pages7
JournalJournal of Pediatrics
Volume137
Issue number6
DOIs
StatePublished - 2000

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Sweat
Cystic Fibrosis
Cyclic AMP
Adrenergic Agents
Cholinergic Agents
Methacholine Chloride
Heterozygote
Forearm
Intradermal Injections
Aminophylline
Sweat Glands
Sweating
Atropine
Isoproterenol
Chlorides
Fibrosis
Phenotype
Injections

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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A simplified cyclic adenosine monophosphate-mediated sweat rate test for quantitative measure of cystic fibrosis transmembrane regulator (CFTR) function. / Callen, Amy; Diener-West, Marie; Zeitlin, Pamela L.; Rubenstein, Ronald C.

In: Journal of Pediatrics, Vol. 137, No. 6, 2000, p. 849-855.

Research output: Contribution to journalArticle

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abstract = "Objective: Sweat production is stimulated by both cholinergic and β-adrenergic pathways in the sweat gland secretory coil. β-Adrenergic pathwav-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 β-adrenergic sweat rate discriminates among 3 different CFTR phenotypes - CE heterozygote CF carriers, and non-CF. Study design: Intradermal injection of a mixture of 50 μmol/L isoproterenol, 5 mmol/L aminophylline (to potentiate the β-adrenergic stimulation), and 140 μmol/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. Results and 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-CE 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.",
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