Muscarinic regulation of potassium transport in a human submandibular epithelial cell line.
Results of previous studies suggest that the transport of K+ by salivary ducts is under muscarinic control. The mechanisms by which this regulation occurs have not been well defined, however. In this paper, we describe mechanisms involved in the muscarinic regulation of K+ (86Rb) transport in HSG-PA, an epithelial cell line derived from human submandibular gland duct. Stimulation of HSG-PA cells by carbachol, a muscarinic agonist, increases both 86Rb influx and efflux, which results in a decrease in the equilibrium content of 86Rb within the cells. Increases in both fluxes are dose dependent with respect to carbachol concentration, and both responses can be blocked by atropine, a muscarinic antagonist. The carbachol-stimulated 86Rb fluxes appear to be calcium dependent since 1) the calcium ionophore A23187 increases 86Rb fluxes in these cells, 2) cells loaded with 1,2-bis(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA; a calcium chelator) exhibit a reduced ability to respond to carbachol stimulation, and 3) removal of extracellular calcium concentration reduces the carbachol-stimulated effects. Treatment of HSG-PA cells with 10(-7) M phorbol myristate acetate (PMA) partially blocks the carbachol-stimulated changes in 86Rb fluxes, suggesting that protein kinase C plays a role in this response. PMA also partially blocks A23187-stimulated 86Rb influx, suggesting that activation of protein kinase C inhibits muscarinic-stimulated K+ influx by blocking either the Ca2+ signal (X. He, X. Wu, and B.J. Baum. Biochem. Biophys. Res. Commun. 152: 1062-1069, 1988), steps subsequent to this effect, or both.(ABSTRACT TRUNCATED AT 250 WORDS)
Ship
J A
JA
Clinical Investigation and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Patton
L L
LL
Wellner
R B
RB
D001285:Atropine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D015398:Signal Transduction; D013363:Submandibular Gland / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D000001:Calcimycin; D004533:Egtazic Acid; D019789:Tetraethylammonium; D001285:Atropine; D002217:Carbachol; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D012413:Rubidium; D011188:Potassium