Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jun;73(6):1763–1771. doi: 10.1172/JCI111385

Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro.

K Sato, F Sato
PMCID: PMC437089  PMID: 6327771

Abstract

Abnormal ductal NaCl absorption has been known as the only defect in cystic fibrosis (CF) sweat glands. We have fortuitously found that the secretory portion of CF sweat glands is also abnormal in that it failed to show a sweating response to beta adrenergic stimulation (isoproterenol, [ISO]) both in vivo and in vitro. For the in vitro sweat test, eccrine sweat glands were isolated from skin biopsy specimens of the forearm, cannulated, and stimulated to secrete sweat. All 14 isolated CF sweat glands failed to respond to ISO + theophylline (TH, as aminophylline), but 17 of 18 control glands responded with a mean rate (SR) of 1.1 nl/min per gland. Cholinergic responsiveness of isolated CF sweat glands was comparable with that of control glands. The in vivo sweat test was performed by intradermal injection in the forearm of 0.2 ml of 2.4 or 8 X 10(-5) M ISO with or without 10(-2) M TH (and 1.4 X 10(-4) M atropine as a necessary anticholinergic agent). The beads of sweat secreted into the oil-filled sweat collection ring glued to the skin were then collected with a glass capillary under a stereomicroscope. Of 28 CF patients, 26 failed to show a secretory response to intradermal injection of ISO + TH, and 2 CF patients gave SR of less than 0.007 nl/min per gland in the first test but no response in the repeat test performed later. In contrast, all 35 age- and sex-matched control subjects responded with the mean SR of 0.72 nl/min per gland. Response of CF patients to epinephrine and phenylephrine was comparable with control, indicating that the alpha adrenergic responsiveness of CF sweat glands is not defective. A preliminary attempt was made to determine tissue cyclic AMP accumulation by radioimmunoassay in isolated sweat glands. No significant difference was observed between CF and control glands in their maximal accumulation of tissue cAMP in response to ISO or ISO + TH, except that the rise time of ISO + TH-induced cAMP accumulation in CF glands was significantly slower during the first 5 min of incubation. The data suggest that beta adrenergic regulation is abnormal in CF sweat glands and justifies further investigations into the mechanism of beta adrenergic regulation of the eccrine sweat gland in both normal and CF subjects.

Full text

PDF
1763

Images in this article

1764Image
on p.1764
1764Image
on p.1764

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRUSILOW S. W. AN ANAEROBIC SWEAT COLLECTION TECHNIQUE. J Lab Clin Med. 1965 Mar;65:513–517. [PubMed] [Google Scholar]
  2. Davis P. B., Braunstein M., Jay C. Decreased adenosine 3':5'-monophosphate response to isoproterenol in cystic fibrosis leukocytes. Pediatr Res. 1978 Jun;12(6):703–707. doi: 10.1203/00006450-197806000-00005. [DOI] [PubMed] [Google Scholar]
  3. Davis P. B., Dieckman L., Boat T. F., Stern R. C., Doershuk C. F. Beta adrenergic receptors in lymphocytes and granulocytes from patients with cystic fibrosis. J Clin Invest. 1983 Jun;71(6):1787–1795. doi: 10.1172/JCI110934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis P. B., Shelhamer J. R., Kaliner M. Abnormal adrenergic and cholinergic sensitivity in cystic fibrosis. N Engl J Med. 1980 Jun 26;302(26):1453–1456. doi: 10.1056/NEJM198006263022605. [DOI] [PubMed] [Google Scholar]
  5. Galant S. P., Norton L., Herbst J., Wood C. Impaired beta adrenergic receptor binding and function in cystic fibrosis neutrophils. J Clin Invest. 1981 Jul;68(1):253–258. doi: 10.1172/JCI110241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harper J. F., Brooker G. Alcohol potentiation of isoproterenol-stimulated cyclic AMP accumulation in rat parotid. J Cyclic Nucleotide Res. 1980;6(1):51–62. [PubMed] [Google Scholar]
  7. Mangos J. A. Microperfusion study of the sweat gland abnormality in cystic fibrosis. Tex Rep Biol Med. 1973 Winter;31(4):651–663. [PubMed] [Google Scholar]
  8. Martinez J. R., Adelstein E., Quissel D., Barbero G. J. The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure. Pediatr Res. 1975 May;9(5):463–469. doi: 10.1203/00006450-197505000-00001. [DOI] [PubMed] [Google Scholar]
  9. Martinez J. R., Martinez A. M., Garrett L., Korman P. Chronically reserpinized rat as a model for cystic fibrosis: Na+ transport inhibitory effect in submaxillary saliva. Pediatr Res. 1979 Oct;13(10):1156–1159. doi: 10.1203/00006450-197910000-00015. [DOI] [PubMed] [Google Scholar]
  10. RANDALL W. C., KIMURA K. K. The pharmacology of sweating. Pharmacol Rev. 1955 Sep;7(3):365–397. [PubMed] [Google Scholar]
  11. Sato K., Sato F. Cholinergic potentiation of isoproterenol-induced cAMP level in sweat gland. Am J Physiol. 1983 Sep;245(3):C189–C195. doi: 10.1152/ajpcell.1983.245.3.C189. [DOI] [PubMed] [Google Scholar]
  12. Sato K., Sato F. Cyclic AMP accumulation in the beta adrenergic mechanism of eccrine sweat secretion. Pflugers Arch. 1981 Apr;390(1):49–53. doi: 10.1007/BF00582710. [DOI] [PubMed] [Google Scholar]
  13. Sato K., Sato F. Individual variations in structure and function of human eccrine sweat gland. Am J Physiol. 1983 Aug;245(2):R203–R208. doi: 10.1152/ajpregu.1983.245.2.R203. [DOI] [PubMed] [Google Scholar]
  14. Sato K., Sato F. Role of calcium in cholinergic and adrenergic mechanisms of eccrine sweat secretion. Am J Physiol. 1981 Sep;241(3):C113–C120. doi: 10.1152/ajpcell.1981.241.3.C113. [DOI] [PubMed] [Google Scholar]
  15. Sato K. The physiology, pharmacology, and biochemistry of the eccrine sweat gland. Rev Physiol Biochem Pharmacol. 1977;79:51–131. doi: 10.1007/BFb0037089. [DOI] [PubMed] [Google Scholar]
  16. Schulz I. J. Micropuncture studies of the sweat formation in cystic fibrosis patients. J Clin Invest. 1969 Aug;48(8):1470–1477. doi: 10.1172/JCI106113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. di Sant'Agnese P. A., Davis P. B. Research in cystic fibrosis (third of three parts). N Engl J Med. 1976 Sep 9;295(11):597–602. doi: 10.1056/NEJM197609092951105. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES