Ryanodine- and cyclopiazonic acid-sensitive components in human vas deferens contractions to noradrenaline

1 The role of calcium stores in noradrenaline- (NA) and caffeine-induced contractions of human vas deferens were investigated using ryanodine and cyclopiazonic acid (CPA) in the presence of the calcium antagonist, nifedipine (1 mu M) or in calcium-free/EGTA (1 mM) medium. 2 In either media, NA (100 mu M) evoked biphasic contractions of longitudinal muscle and tonic circular muscle contractions. Caffeine (20 mM) evoked longitudinal but not circular muscle contractions. 3 Ryanodine (1-30 mu M) or CPA (1-30 mu M) inhibited contractions of circular muscle, and the initial but not secondary component of longitudinal muscle contraction to NA. 4 In the presence of nifedipine, pre-exposure to caffeine caused a potentiation of circular muscle, and the initial but not secondary longitudinal muscle contractions to NA. The presence of ryanodine or CPA during the caffeine pre-exposures effectively blocked the potentiation of the initial component and reduced the secondary component of the subsequent responses to NA in longitudinal muscle. 5 In calcium-free media, caffeine pre-exposures had little effect on subsequent NA-induced contractions in circular muscle, but reduced both components in longitudinal muscle. The presence of ryanodine or CPA during caffeine pre-exposures produced no further effects on either component of the subsequent NA-induced contraction in longitudinal muscle. 6 In the presence of nifedipine or in calcium-free media, repeated applications of caffeine evoked contractions in longitudinal muscle which were not blocked by either ryanodine or CPA. 7 These results suggest that circular muscle contraction by NA and the initial component of longitudinal muscle to NA both utilize an intracellular pool of calcium that is triggered via a ryanodine-sensitive mechanism and replenished via a CPA-sensitive Ca2+-ATPase. 8 In longitudinal muscle, both the secondary component of its response to NA and contraction to caffeine appear to involve an unusual but pharmacologically distinct (ryanodine- and CPA-insensitive) pathway. 9 The quiescence to caffeine of circular muscle may be caused by a relative absence of the ryanodine- and CPA-insensitive pathway.