EVIDENCE FOR 2 TYPES OF INTERNAL CA-2+ STORES IN CANINE MESENTERIC-ARTERY WITH DIFFERENT REFILLING MECHANISMS

Novel transient biphasic responses of the dog mesenteric artery to phenylephrine hydrochloride (PE, 10-mu-M) in Ca2+-free medium containing 50-mu-M ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) have been analyzed. The initial component was significantly inhibited by ryanodine (30-100-mu-M), an agonist enhancing Ca2+ release from the sarcoplasmic reticulum, whereas the second was significantly inhibited by nifedipine (1-mu-M), an L-type Ca2+ channel antagonist, or EGTA, to chelate Ca2+, and was potentiated by BAY K 8644 (1-mu-M), an L-type Ca2+ channel agonist. After repletion of Ca2+ stores in normal Krebs solution or in high KCl (60 mM) Krebs, the first component was inhibited by cyclopiazonic acid (CPA, 30-mu-M), a putative, reversible, and selective microsomal Ca2+ pump adenosinetriphosphatase inhibitor. BAY K 8644 potentiated the second component in the presence of CPA. The inhibition of the first component by CPA suggests that the refilling ultimately requires the CPA-sensitive Ca2+ pump for Ca2+ resequestration. However, the second component may refill by a CPA-independent route opened by BAY K 8644. These results, taken as a whole, indicate that the biphasic PE response in Ca2+-free medium may reflect compartmentalization of Ca2+ storage related to the different routes of refilling.