Assessing accurately the pH of axillary eccrine sweat is of vital importance in the antiperspirant industry. Eccrine sweat pH is a critical parameter in determining the effectiveness of antiperspirants; antiperspirant salts dissolve in sweat and diffuse into the sweat glands, where the resultant acidic solution hydrolyses in more alkaline sweat forming an amorphous metal hydroxide gel, thereby restricting the flow of eccrine sweat. Comparison of the skin surface and sweat pH of males and females reported in the literature shows that, although consistent male/female differences have been observed on the forearm, determination of significant gender-based pH differences across other sites are less conclusive. Studies on the back and infra-mammary regions exhibited significant gender differences in skin surface pH, whereas those on the forehead, cheek, neck and inguinal area showed no such difference. With regard to the axilla specifically, four studies have been reported, three showing no significant difference in axillary skin surface pH and one indicating that females have an eccrine sweat pH of 7 and males have a sweat pH of 5.6. This paper describes a series of carefully controlled studies aimed at assessing potential gender differences in eccrine sweat and skin surface pH following exposure to a variety of temperature, humidity and time conditions. The results highlight the importance of controlling precisely the time of investigation, site of measurement and, most importantly, the necessity to pre-equilibrate samples in 40 mmHg carbon dioxide (equivalent to arterial CO(2) tension (pCO2)) before determining sweat pH. When these parameters are controlled no gender differences in axillary sweat or skin surface pH are observed. Large differences in eccrine sweat and skin surface pH are found, however, between the vault (hairy region) and fossa (non-hairy region) of the axilla.

Using an anti-NHE1 antibody, we demonstrate the presence of a Na+/H+ exchanger of isoform 1 (NHE1) in the human eccrine sweat duct. A strong staining was observed at the basolateral membrane of the outer cell layer (NHE1basal), at the junction between inner and outer cells layers (NHE1inter), and along the lateral membranes (NHE1later) of all cells of the duct. At the luminal membrane, no staining was demonstrated either for NHE1 or NHE3. To investigate Na+/H+ mediated proton transport, straight sweat duct portions were isolated and perfused in vitro under HCO3-free conditions. In the presence of basolateral 5-ethyl-N-isopropyl amiloride (EIPA), an acidification of 0.29 +/- 0.03 pH units was observed, whereas no effect was observed with luminal EIPA. Bath sodium removal generated a stronger acidification (0.41 +/- 0.09 pH units). Removal of luminal sodium (in the absence or presence of basolateral EIPA), or low luminal chloride, led to an alkalinization, presumably due to a decrease in intracellular sodium, strongly suggesting functional activity of NHE1inter. We therefore conclude that in the sweat duct, NHE1 plays a major role in intracellular pH regulation.

.-We investigated for the presence of a vacuolar-type H ϩ -ATPase (V-ATPase) in the human eccrine sweat duct (SD). With the use of immunocytochemistry, an anti-VATPase antibody showed a strong staining at the apical membrane and a weaker one in the cytoplasm. Cold preservation followed by rewarming did not alter this staining pattern. With the use of the pH-sensitive dye 2Ј,7Ј-bis(2-carboxyethyl)-5(6)-carboxyfluorescein on isolated and perfused straight SD under HCO 3 Ϫ -free conditions and in the absence of Na ϩ , proton extrusion was determined from the recovery rate of intracellular pH (dpHi/dt) following an acid load. Oligomycin (25 M), an inhibitor of F-type ATPases, decreased dpHi/dt by 88 Ϯ 6%, suggesting a role for an ATP-dependent process involved in pHi recovery. Moreover, dpHi/dt was inhibited at 95 Ϯ 3% by 100 nM luminal concanamycin A, a specific inhibitor of V-ATPases, whereas 10 M bafilomycin A1, another specific inhibitor of V-ATPases, was required to decrease dpHi/dt by 73%. These results strongly suggest that a V-ATPase is involved in proton secretion in the human eccrine SD. proton pump; intracellular pH measurement; concanamycin A; bafilomycin A1; oligomycin THE SECRETORY PORTION of the eccrine sweat gland generates a fluid called the primary secretion. The composition of this isotonic fluid is similar to an ultrafiltrate of the plasma and has a pH of 7.4. However, as it flows through the ductal portion of the gland, this fluid is modified by the reabsorption of solutes such as Na ϩ , Cl Ϫ , lactate, and HCO 3 Ϫ , leaving a hypotonic sweat (4, 32). Current models of ionic transport in the human eccrine sweat duct propose the presence of luminally located Na ϩ and Cl Ϫ channels and basolaterally located Na ϩ -K ϩ -ATPase, as well as K ϩ and Cl Ϫ channels (4,2,35,32,33,36). The pH of final sweat is a function of sweat rate, being as acidic as pH 5 when the sweat rate is low and increasing as sweat rate increases (22). The acidity of sweat implies that sweat duct cells secrete protons across the apical membrane, and the presence of an electrogenic proton-secreting pump at this membrane has been proposed (3, 27, 34). Indeed, vacuolar-type H ϩ -ATPases (V-ATPases) have been shown to be responsible for the acidification in many organelles of eukaryotic cells, including clathrin-coated vesicles, lysosomes, endosomes, and vacuoles of plants and fungi (31). Moreover, V-ATPases are highly expressed in the apical membrane of specialized epithelial cells in the kidney (13, 24), epididymis, and vas deferens (14), where they play a major role in the acidification of urine and luminal fluid of the reproductive tract (11,16,12,23).Recently, in the sweat duct, we have demonstrated by both immunolocalization and intracellular pH (pH i ) measurements that both Na ϩ /H ϩ exchanger isoforms 1 (NHE1) and 3 (NHE3) were absent from the luminal membrane, whereas NHE1 was present at the basolateral membrane (25). In addition, an immunolocalization study showed the presence of an apical V-ATPase (7).Therefore, the aim ...

Sweat and skin surface pH are critical parameters in determining the performance of antiperspirants. The mechanism of action, the so-called 'plug theory' first proposed by Reller and Luedders, involves the expression of eccrine sweat onto the surface of the skin into which the solid antiperspirant salts, typically an aluminium chlorohydrate or zirconium aluminium glycine, dissolve. The resultant acidic 'solution' then diffuses with time into the sweat glands, where it hydrolyses in more alkaline sweat and forms an amorphous metal hydroxide agglomerate that physically plugs the ducts some 20-100 mum into the glands. It is therefore important to understand whether diurnal variations in skin surface pH exist in the axilla, as these may influence strongly the time of day at which antiperspirant should be applied in order to yield maximal protection. Clinical studies demonstrate a significant fall in axillary skin surface pH between the morning (pH = 5.87 +/- 0.23) and the evening (pH = 5.49 +/- 0.23). This diurnal variation in skin surface pH suggests that antiperspirant efficacy will be optimal when products are applied in the morning. In addition, the data suggest a circadian rhythm in axillary skin barrier function, indicating that chronopharmacology, the timing of administration of medication, could be used to optimize treatment of axillary hyperhidrotics using topical administration of anticholinergic drugs.

One of ethanol's actions after acute exposure is anticonvulsant activity whereas withdrawal from chronic ethanol exposure increases convulsant activity. An increase in neuronal transmission in the GABAergic pathways from striatum to the substantia nigra (SN) and a decrease in GABAergic transmission from SN to superior colliculus (SC) both appear to play a major role in inhibiting seizure propagation. If this is the case, then the changes in seizure sensitivity caused by ethanol may be expected to affect GABAergic transmission in opposite ways in SN and SC. We measured the effects of in vitro ethanol on pre- and postsynaptic indices of GABA transmission using SN and SC tissue from both ethanol-naive rats and rats given ethanol in their drinking water for 24 days and then withdrawn for 24 hr, a treatment that decreases seizure latency. While ethanol inhibited 3H-GABA release from slices of SC at low concentrations (20-100 nM), much higher concentrations were required to inhibit release from SN (100-500 mM). In fact, release from SN was increased by low concentrations of ethanol. Ethanol in vitro (20-1000 mM) also inhibited specific binding of 35S-TBPS to the GABAA receptor but this effect was similar in both potency and efficacy in SC and SN. Next, the in vitro effects of ethanol were measured in rats that had consumed an average of 9.8 g ethanol/kg body weight/day and were then withdrawn for 24 hr. Ethanol inhibition of 3H-GABA release from SC was significantly less in ethanol-treated rats compared to controls whereas the inhibitory effect of ethanol was increased in SN from ethanol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)