Effect of carbachol and prostaglandin E2 on chloride secretion and signal transduction in the exocrine glands of frog skin (Rana esculenta).
Carbachol (CCH) increased the short-circuit current across frog skin glands in a biphasic manner, which coincided with an increase in the transepithelial Cl- net flux. CCH also induced a biphasic increase in [Ca2+]i. Both these responses were mediated via muscarinic receptors. The plateau phase of the CCH-induced Cl- secretion was modestly inhibited by indomethacin and unaffected by tetrodotoxin or tetrodotoxin plus indomethacin, indicating that CCH can increase Cl- secretion directly via receptors on the secretory cells. Prostaglandin E2 (PGE2) increased secretion and cAMP production, indicating expression of EP2 and/or EP4 receptors. PGE2 failed to increase [Ca2+]i ruling out involvement of EP1 receptors. The secretory response to CCH was potentiated by prestimulation with PGE2, and it was investigated whether this potentiation is caused by interaction at the level of the messengers involved. Stimulation by CCH plus PGE2 failed to stimulate cAMP production further than PGE2 alone. Addition of PGE2 during the CCH-elevated [Ca2+]i plateau phase in most cases reduced the level of [Ca2+]i. These data show that the synergy between CCH and PGE2 is not based on interactions at the intracellular messenger level.
Nielsen
M S
MS
Biochemical Department, August Krogh Institute, Copenhagen University, Denmark.
Nielsen
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D005088:Exocrine Glands / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009424:Nervous System Physiological Phenomena; D011453:Prostaglandins / Q000378:metabolism; D011893:Rana esculenta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000187:drug effects*
D002712:Chlorides; D018679:Cholinergic Agonists; D011453:Prostaglandins; D011976:Receptors, Muscarinic; D002217:Carbachol; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium