title: A capacitative Ca2+ influx is required for sustained fluid secretion in sublingual mucous acini.
abstract: The Ca2+ dependence of muscarinic-induced fluid and electrolyte secretion was studied using rat sublingual mucous gland preparations. During stimulation, secretions from vascularly perfused glands were totally inhibited when perfused with a Ca(2+)-free medium. Fluid secretion correlated with sustained losses of 42K+ and 36Cl- content and sustained increases in 22Na+ content and the intracellular free Ca2+ concentration ([Ca2+]i) in fura-2-loaded acini. The magnitudes of the initial agonist-induced changes in Na+, K+, and Cl- content and [Ca2+]i were unaltered in a Ca(2+)-free medium, whereas extracellular Ca2+ removal resulted in the recovery of these ions during the sustained phase to pre-stimulation levels. The recovery of Cl- content induced by Ca2+ depletion was totally blocked in the presence of bumetanide, an inhibitor of Na(+)-K(+)-2Cl- cotransport, while 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of anion exchange, did not influence Cl- recovery in a HCO(3-)-containing solution (25 mM NaHCO3, 5% CO2). The stimulated increase in [Ca2+]i was not inhibited by the addition of voltage-activated Ca2+ channel blockers (D 888, nifedipine, and diltiazem) or in a Na(+)-free medium. Studies using the quench of fura-2 by Mn2+ as an index of Ca2+ influx and thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase, indicate that a capacitative Ca2+ entry pathway mediates Ca2+ entry during stimulation. The above data demonstrate that Ca2+ uptake, which is dependent on the refill status of the agonist-sensitive intracellular Ca2+ pool, is a prerequisite for sustained muscarinic-induced fluid and electrolyte secretion in the rat sublingual mucous gland.
authors.affiliation: Department of Dental Research, University of Rochester, New York 14642.
authors.forename: J E
authors.initials: JE
authors.lastname: Melvin
authors.forename: L
authors.initials: L
authors.lastname: Koek
authors.forename: G H
authors.initials: GH
authors.lastname: Zhang
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D004553:Electric Conductivity; D007700:Kinetics; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013361:Sublingual Gland / Q000378:metabolism*; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002712:Chlorides; D002034:Bumetanide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C043184:4-desmethoxyverapamil; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D002118:Calcium