RT Journal Article SR Electronic T1 The Putative Phospholipase C Inhibitor U73122 and Its Negative Control, U73343, Elicit Unexpected Effects on the Rabbit Parietal Cell JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1379 OP 1388 VO 282 IS 3 A1 Muto, Yuko A1 Nagao, Taku A1 Urushidani, Tetsuro YR 1997 UL http://jpet.aspetjournals.org/content/282/3/1379.abstract AB In order to elucidate the role of phospholipase C (PLC) in gastric acid secretion, we used U73122, a commonly employed specific inhibitor of receptor-mediated PLC, and its negative control, U73343. Although 10 μM U73122 inhibited the increase in [Ca++]i induced by U46619 in rabbit platelets, Ca++ transients in the rabbit parietal cells elicited by histamine and carbachol were both resistant to the inhibitor. U73122 augmented the acid secretion of isolated gastric glands stimulated by histamine, carbachol and dbcAMP, possibly through its indirect Ca++-releasing effect on the intracellular calcium store. U73122 potently inhibited K+-p-nitrophenylphosphatase without affecting overall H+,K+-ATPase activity. On the other hand, the negative control, U73343, strongly inhibited the acid secretion stimulated by all agonists tested. The inhibitory effect was also evident on digitonin-permeabilized glands and on the proton gradient of gastric vesicles. U73343 itself is not a proton pump inhibitor, so it was considered a protonophore. In conclusion, the widely used PLC-inhibitor, U73122, and its negative control, U73343, are both useless as tools for analyzing the role of PLC in rabbit parietal cells. The former is ineffective on gastric PLC and works as an intracellular calcium releaser, and the latter works as a protonophore. The American Society for Pharmacology and Experimental Therapeutics