Roles of Ca2+ and Na+ on the modulation of antidiuretic hormone action on urea permeability in toad urinary bladder.
The present studies probe the role of Ca2+ and Na+ in the stimulation-permeability coupling sequences by which antidiuretic hormone (ADH) induces a cyclic AMP (cAMP)-mediated increase in urea permeability in toad urinary bladder. The following results were obtained: (a) Removal of mucosal Na+ or Ca2+ or deletion of serosal Ca2+ did not modify ADH action. (b) Reduction of the serosal Na+ concentration to less than 50 mM inhibited the effects of both ADH and cAMP. The minimal concentration of serosal Na+ needed for the hormone to elicit its maximal effect was reduced to approximately 10 mM if serosal Ca2+ was concomitantly deleted. (c) The Na+ ionophore monensin produced an inhibition of ADH and cAMP actions that was dependent on the presence of Na+ and Ca2+ in the serosa. (d) The Ca2+ ionophore A23187 produced a serosal Ca2+-dependent inhibition of ADH effect and did not modify cAMP action. (e) Carbachol, which increases Ca2+ uptake to the same extent that A23187 does, had no effect on ADH action. (f) Quinidine, which releases Ca2+ from intracellular stores, produced a large inhibition of the action of ADH but not that of cAMP; the inhibition was greatly reduced if serosal Ca2+ was deleted. (g) Dinitrophenol and iodoacetate, which also release Ca2+ from intracellular pools, had no effect on ADH action. (h) The Ca2+ channel blocker diltiazem had no effect on ADH action and did not modify the inhibitions produced by deletion of serosal Na+ or monensin. (i) The cyclooxygenase inhibitor indomethacin partially removed the inhibition produced by deletion of serosal Na+ and almost completely impeded the inhibitions produced by either monensin or A23187. It is concluded: (a) Extracellular Ca2+, Na+ transport rates, and serosal Na+, in concentrations between 10 and 110 mM, have no participation in modulating the increase in urea permeability produced by ADH. (b) Increases in cytosolic Ca2+ activity, which are capable of inhibiting the effect of ADH on urea permeability at pre- and/or post-cAMP steps, seem to be highly compartmentalized. (c) Endogenous prostaglandins might play a role in the inhibitions produced by absence of serosal Na+, monensin, or A23187.
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002024:Bufo marinus; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008985:Monensin / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism / Q000502:physiology*; D014508:Urea / Q000378:metabolism*; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*
D004140:Dinitrophenols; D007461:Iodoacetates; D001127:Arginine Vasopressin; D000001:Calcimycin; D014508:Urea; D002217:Carbachol; D008985:Monensin; D012964:Sodium; D004110:Diltiazem; D011802:Quinidine; D002118:Calcium; D019807:Iodoacetic Acid; D007213:Indomethacin