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.

The mechanisms underlying variations in perspiration rate at the glandular level are still poorly understood. Human eccrine sweat glands were dissected from the back of 12 adults, cannulated, and stimulated in vitro with methacholine (Mch). The maximal sweat rate and pKA for Mch determined from the dose-response curve for each individual were compared with the anatomic dimensions of the isolated secretory tubules. There was significant correlation between Mch sensitivity (pKA) and the size of the sweat gland, sweat rate per gland, sweat rate per unit length of the secretory tubule, and sweat rate per unit glandular volume. The sweat glands from individuals judged to be poor sweaters exhibited smaller size, lower secretory activity both in vivo and in vitro, and decreased Mch sensitivity compared with glands from physically fit individuals. We conclude that the increased Mch sensitivity and glandular hypertrophy are the two important features of functionally active sweat glands and infer that these parameters could improve as a result of acclimatization to physical exercise and/or heat.

Evidence is presented that in adult human axillae there exists a third type of sweat gland tentatively designated as the apoeccrine sweat gland. This type of gland shows a segmental or diffuse apocrinelike dilatation of its secretory tubule but has a long and thin duct which does not open into a hair follicle. The electron microscopy of its dilated segment is often indistinguishable from that of the classical apocrine gland. The less remarkably dilated segment of the apoeccrine gland tends to retain intercellular canaliculi and/or dark cells. These apoeccrine glands are consistently present in adult human axillae regardless of sex or race. In the axillae of the two 6-yr-old subjects, both classical apocrine and eccrine glands were present but no apoeccrine glands were found. Between 8-14 yr of age, the number of large eccrine glands with or without partial segmental dilatation gradually increased. At 16-18 yr of age, the number of apoeccrine glands increased to as high as 45% of the total axillary glands. The data support the notion that apoeccrine glands develop during puberty in the axillae from eccrine or eccrinelike sweat glands.

In an attempt to devise a method for collecting large volumes of thermally induced sweat with less epidermal contamination and evaporative water loss, we developed an anaerobic sweat collector by using a sheet of polyethylene film placed over a thin layer of Vaseline and paraffin oil on the skin. To test the validity of the new method, sweat samples collected every 5 min from the new collector (sweat A) were compared with those obtained from a second collector using no oil (sweat B) and scraped sweat for concentrations of adenosine 3',5'-cyclic monophosphate (cAMP), protein, glucose, urea, lactic acid, calcium, sodium, potassium, and cholesterol. The concentration of sweat ingredients in scraped sweat was often far greater than could be expected from evaporative water loss alone. When compared with sweat A, sweat B also had higher concentrations of these ingredients in the initial samples, indicating epidermal contamination, which was especially marked in cAMP, protein, urea, cholesterol, and calcium. Concomitant with a rise in plasma glucose following the administration of a glucose bolus, the sweat glucose significantly increased, indicating the plasma as a major source of sweat glucose. We conclude that the new sweat collector is instrumental in collecting large volumes of the cleanest possible human sweat.

Three adult male patas monkeys (11-15 kg) were heat acclimated by continuous exposure to an ambient temperature of 33 +/- 1 degree C at 13% relative humidity for 9 mo. During the last month, they were also exposed to 45 degrees C at 10% relative humidity for 4 h/day and 5 days/wk. Before and after 3 wk of acclimation, the animals were given a heat-tolerance test in which rectal (Tre) and mean skin (Tsk) temperatures, heart rate, and sweat rate (msw) were monitored during a 90-min exposure to 45 degrees C heat with 24% relative humidity under lenperone (1.0-1.4 mg/kg im) tranquilization. Maximal in vivo msw was also determined in response to subcutaneous injections (1 and 10% solutions) of methacholine (MCh). Before and after 9 wk and 9 mo of acclimation, sweat glands were dissected from biopsy specimens of the lateral calf, cannulated, and stimulated in vitro with MCh. Morphological measurements of isolated tubules were compared with maximal secretory rates produced by MCh stimulation. Three weeks of acclimation 1) reduced Tre and Tsk and increased msw during the heat tolerance test and 2) significantly increased maximal msw in response to MCh stimulation. Acclimation also increased (P less than 0.05) sweat gland size, as measured by tubular length and tubular volume. Maximal in vitro msw produced by MCh stimulation and msw per unit length of secretory coil also increased significantly. We conclude that heat acclimation increases the size of eccrine sweat glands and that these larger glands produce more sweat. They are also more efficient because they produce more sweat per unit length of secretory coil.

Pharmacologic responsiveness of the eccrine sweat gland has never been studied under well-defined in vitro experimental conditions. Using isolated cannulated single monkey palm eccrine sweat glands, the dose response to both cholinergic and alpha- and beta-adrenergic agents and the effects of various antagonists on agonists were studied. The maximal sweat rate was highest after stimulation with cholinergic agonists, was lower with the beta-adrenergic agonist, and was least with the alpha-adrenergic agonist. Each secretory response was inhibited by its specific antagonist. Attempts to demonstrate the spare receptor, if any, by means of preincubation of the glands with N-(2-chlorethyl)dibenzylamine (Dibenamine) were unsuccessful. From the hyperbolic dose-response curves the values for KA and KB, dissociation constants for agonists and antagonists, respectively, were thus tentatively estimated according to Clark's classical receptor theory. Schild plots for each agonist-antagonist interaction produced straight lines with slopes of near unity, indicating the adequacy of the methodology. It was concluded that the isolated eccrine sweat glands retain their pharmacologic viability in vitro and show responsiveness to cholinergic as well as both alpha- and beta-adrenergic stimulations.

Functional characteristics of isolated single human axillary apoeccrine sweat glands have been studied using in vitro sweat induction methods. Sustained copious clear fluid secretion was evoked by methacholine (MCh), epinephrine (EP), isoproterenol (ISO), and phenylephrine (PL) in decreasing order in a pharmacologically specific manner. Apoeccrine glands showed a higher cholinergic sensitivity than eccrine sweat glands, as shown by the apparent association constant for MCh of 2.7 X 10(-7) M compared with 2.1 X 10(-6) M for the axillary eccrine sweat gland. The average total sweat rate of the apoeccrine gland for a 30-min period was sevenfold higher than that of the eccrine sweat gland. In contrast, isolated apocrine glands showed intermittent pulsatile turbid sweat secretion in response to MCh or EP. The Na+ and K+ concentration of apoeccrine glands was nearly isotonic, whereas those of apocrine sweat was 120-140 mM for Na+ and 10-20 mM for K+. Apoeccrine ductal Na+ absorption was also observed in the apoeccrine glands and was no more efficient than that of the axillary eccrine sweat gland. Thus apoeccrine sweat glands are functionally and pharmacologically distinct from axillary apocrine glands and significantly contribute to overall axillary sweating in humans.

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