Octanol blocks fluid secretion by inhibition of capacitative calcium entry in rat mandibular salivary acinar cells.
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.
Kim
Y J
YJ
Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea.
Elliott
A C
AC
Moon
S J
SJ
Lee
S I
SI
Seo
J T
JT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008334:Mandible; D000442:Octanols / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000166:cytology
D000442:Octanols; D002217:Carbachol; D002118:Calcium