Rapid secretagogue-induced activation of Na+H+ exchange in rat parotid acinar cells. Possible interrelationship between volume regulation and stimulus-secretion coupling.
We demonstrate a rapid activation of the Na+/H+ exchanger in intact rat parotid acini in response to muscarinic (carbachol; K1/2 = 0.4 microM) and alpha-adrenergic (epinephrine; K1/2 = 0.1 microM) stimulation. This rapid activation is apparently distinct from the relatively "slow" activation of the exchanger (t1/2 greater than or equal to 5 min) reported previously (Manganel, M., and Turner, R. J. (1989) J. Membr. Biol. 111, 191-198). This rapid activation is not produced by treatment of acini with active diacylglycerol analogues nor prevented by protein kinase inhibitors, arguing against the involvement of protein kinase C-dependent processes. Stimulation of the exchanger is, however, produced by concentrations of ionomycin which yield intracellular calcium levels in the physiologic (secretagogue-induced) range. In addition, chelation of intracellular calcium with 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid blocks the effect of carbachol, but calmodulin antagonists are without effect. The possibility that the rapid activation of the Na+/H+ exchanger may be associated with cell shrinkage arising from carbachol-induced calcium mobilization is explored. In support of this suggestion we present evidence that: (i) the Na+/H+ exchanger is stimulated by shrinkage of these cells, (ii) the carbachol dose dependence of Na+/H+ exchange activation correlates well with that of shrinkage (but not with that of intracellular calcium levels), and (iii) maneuvers which blunt carbachol- or calcium-induced shrinkage also blunt activation of the exchanger. We suggest that this osmoregulatory response may play an important role in maintaining ionic homeostasis during the acinar fluid secretory process.
Manganel
M
M
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Turner
R J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D018999:Charybdotoxin; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009995:Osmosis; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012604:Scorpion Venoms / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D015854:Up-Regulation
D002352:Carrier Proteins; D012604:Scorpion Venoms; D017923:Sodium-Hydrogen Exchangers; D018999:Charybdotoxin; D002217:Carbachol; D011493:Protein Kinase C; D002118:Calcium; D004837:Epinephrine