title: Effects of pilocarpine on the secretory acinar cells in human submandibular glands.
abstract: 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.
authors.affiliation: Department of Physiology, Seoul National University and Dental Research Institute, Seoul 110-749, South Korea.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Li
authors.forename: Soojung
authors.initials: S
authors.lastname: Lee
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seog-Bae
authors.initials: SB
authors.lastname: Oh
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung Chang
authors.initials: SC
authors.lastname: Chung
authors.forename: Joong-Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
mesh_terms: 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
chemical_list: 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