Effects of pilocarpine on the secretory acinar cells in human submandibular glands.
Pilocarpine has been used as a choice of drugs for treatment of impaired salivary flow. Although considerable data are available as to the stimulatory effect of pilocarpine on the salivary secretion in human, its underlying mechanism, at the cellular level, has not been rigorously studied. In this experiment, we studied the effect of pilocarpine on the ion channel activity, cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and aquaporin (AQP)-5 expression, which play key roles in the secretary process and determine the capacity of fluid secretion. In human submandibular gland (SMG) acinar cells, 10(-5) M pilocarpine activated the outward rectifying-current, which was predominantly K(+) selective in the whole cell patch clamp study. The pilocarpine increased [Ca(2+)](i) in a concentration-dependent manner in the range of 10(-6) M to 10(-4) M. We found that both increases of [Ca(2+)](i) and outward rectifying- K(+) current were inhibited by 10(-5) M U-73122, a specific phospholipase C inhibitor. The magnitudes of pilocarpine-induced [Ca(2+)](i) transients were approximately 55% lower than those with the same concentration of carbachol (CCh). Pilocarpine also increased the amount of AQP-5 protein in the apical membrane (APM) in human SMG acinar cells. Our results suggest that pilocarpine induce salivary secretions in human by activating K(+) channels, increasing [Ca(2+)](i) via phospholipase C dependent pathway, and increasing AQP-5 protein expression in the APM of SMG acinar cells.
Li
Jinchao
J
Department of Physiology, Seoul National University and Dental Research Institute, Seoul 110-749, South Korea.
Lee
Soojung
S
Choi
Se-Young
SY
Lee
Sung Joong
SJ
Oh
Seog-Bae
SB
Lee
Jong-Ho
JH
Chung
Sung Chang
SC
Kim
Joong-Soo
JS
Lee
Jong Heun
JH
Park
Kyungpyo
K
D000328:Adult; D000368:Aged; D051402:Aquaporin 5 / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D051402:Aquaporin 5; D004963:Estrenes; D007473:Ion Channels; D018721:Muscarinic Agonists; D015221:Potassium Channels; D011760:Pyrrolidinones; D010862:Pilocarpine; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; D002217:Carbachol; D010738:Type C Phospholipases; D002118:Calcium