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 μM 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 μM 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.
Bibliographical noteFunding Information:
We wish to thank Dr Sue Goo Rhee, Laboratory of Cell Signalling, National Heart, Lung and Blood Institute, National Institutes of Health, USA for the gift of embryonic fibroblasts. This work was supported by a KOSEF (KOSEF-971-0709-079-1) grant for 1997, and by a British Council Anglo-Korean Collaborative Research Programme (CRP) Grant.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology