Octanol blocks fluid secretion by inhibition of capacitative calcium entry in rat mandibular salivary acinar cells

Abstract

The aliphatic alcohol octanol is thought to modulate enzyme secretion from the exocrine pancreas by the inhibition of gap junction permeability. We have now investigated the effects of octanol on salivary secretion and intracellular calcium concentration ([Ca2+]i), measured in isolated perfused rat mandibular glands and in isolated mandibular acinar cells respectively. Stimulation of perfused glands with 10 microM carbachol (CCh) evoked a rapid increase in fluid secretion followed by a decrease to a sustained elevated level. Application of 1 mM octanol during CCh stimulation inhibited fluid secretion reversibly. In isolated acini, the CCh-induced [Ca2+]i increase was reversibly inhibited by the same concentration of octanol. However, octanol also inhibited the increase in [Ca2+]i in single acinar cells where gap junctions were no longer functional, indicating that octanol directly affected the intracellular Ca2+ signalling pathway. The initial increase in [Ca2+]i induced by 0.5-10 microM CCh, which is due to Ca2+ release from IP3-sensitive Ca2+ stores, was not affected by pretreatment with octanol. In contrast, CCh-, phenylephrine- or thapsigargin-induced Ca2+ entry was almost completely and reversibly inhibited by octanol. Octanol also blocked agonist-evoked Ca2+ entry in pancreatic acinar cells, and thapsigargin-evoked Ca2+ entry in fibroblasts. These data strongly suggest that octanol blocks salivary secretion from mandibular gland by the inhibition of capacitative Ca2+ entry, and raise the possibility that octanol may be a useful tool for inhibiting agonist-evoked Ca2+ entry pathways.

Effects of AlF 4 - and ATP on intracellular calcium dynamics of crypt epithelial cells in mouse small intestine

“…3). Octanol can inhibit gap junctional communication and capacitative Ca 2+ entry (Kim et al 1999). Therefore, the present results indicate that AlF 4 --induced oscillatory fluctuations of [Ca 2+ ] i depend on intercellular communication via gap junctions and Ca 2+ influx.…”

Mechanisms of Connexin-Related Lymphedema

“…Since 18β-GA and other gap junction blockers are not specific for any Cx isoforms 53–55, 76 and also are known to have off-target effects on ion channels 77–79 , we turned to genetic approaches to disrupt Cx function. We first considered Cx45 since it showed robust expression in both human and murine lymphatic vessels (Figure 4B,D).…”

Connexins and secretion

“…show inhibited secretion in the presence of octanol (Kim et al, 1999). To what extent this effect is only due to cell uncoupling remains to be determined, inasmuch as the uncoupling drug also inhibited the capacitive entry of Ca 2+ into salivary acinar cells (Kim et al, 1999).…”

“…show inhibited secretion in the presence of octanol (Kim et al, 1999). To what extent this effect is only due to cell uncoupling remains to be determined, inasmuch as the uncoupling drug also inhibited the capacitive entry of Ca 2+ into salivary acinar cells (Kim et al, 1999). The use of the knock out transgenic mice lacking one or another of the connexins connecting the acinar cells of salivary glands (Nelles et al, 1996; Ott and Willecke, personal communication) should provide some insights into this question.…”