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

Abstract

Abstract. Abnormal ductal NaCi 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 l0-' M ISO with or without 10-2 M TH (and 1.4 X l0-4 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 ofISO + TH, and 2 CF patients gave SR of <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 radioim- The data suggest that beta adrenergic regulation is abnormal in CF sweat glands and justifies further investigations into the mechanism of beta adrenergic regulation ofthe eccrine sweat gland in both normal and CF subjects.

Proceedings of the Physiological Society, 14‐15 February 1992, Bristol Meeting: Communications

“…In addition, intracellular chloride is significantly (P < 0.00009; t test) higher in hypertension. This is consistent with an increase in the activity of the co-transporter, resulting also in the depolarization of membrane potential which we have reported previously (Davis et al 1991 (Sato & Sato, 1984;Bovell et al 1989). In the present experiments we have explored the extent to which such second messenger signals can be evoked in primary cultures of sweat gland epithelial cells (Lee et al 1986) and in a permanent cell line (NCL-SG3) derived from such cells by SV40 transformation (Lee & Dessi, 1989).…”

Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium.

“…USA 82 (1985) 6171 regulation may be faulty. A defect in regulation is suggested by the results of Sato and Sato (19). They found that methacholine induced the same flow rates from normal and CF sweat glands and that isoproterenol caused the same elevation of cyclic AMP in control and CF glands and stimulated sweat secretion in normal glands but did not induce flow from CF glands.…”

Hyposecretion of β-Adrenergically Induced Sweating in Cystic Fibrosis Heterozygotes

“…The protocols were designed to give the most reproducible results in each case, but they have the drawback that comparisons of sweat responses are strictly relative to our procedures: absolute sweat rates, including maximal rates, were not measured. For 0-adrenergic stimulation, sweat was collected once, 40 min after stimulation, to maximize the amount of sweat obtained in each test (most sweating t o P-adrenergic stimulation occurs in the first 20 min following an injection, and is virtually complete after 30 min) (8).…”