ROLES OF CA2-INDUCED CONTRACTIONS IN GUINEA-PIG TRACHEA( INFLUX AND INTRACELLULAR CA2+ RELEASE IN AGONIST)

The contribution of receptor-operated Ca2+ channels (ROCs), voltage-op erated Ca2+ channels (VOCs), and intracellular Ca2+ release to contrac tions induced by a range of stimuli in the guinea pig isolated trachea has been evaluated. In the presence of physiological Ca2+ (1.3 x 10(- 3) M), tissue pretreatment with ethylene glycol-bis(beta-aminoethyl et her)-N,N,N',N' -tetraacetic acid (EGTA) (4 x 10(-3) M for 5 min) marke dly inhibited (> 90%) the contractile responses to a range of agonists . Therefore, under physiological Ca2+ concentration, Ca2+ mobilization from internal stores appeared to make little contribution to maximum contractions. Nifedipine (10(-7) M) or verapamil (10(-5) M) abolished KCl-induced contractions but produced variable inhibition of contracti ons induced by other agonists. The ROC (and VOC) blocker, SK&F 96365 ( 10(-5)-10(-4) M), inhibited both KCl-induced contractions and the nife dipine-insensitive component of contractions induced by acetylcholine (ACh), U46619, or leukotriene D-4 [half maximal inhibitory concentrati on (IC50) values 1.7-3.8 x 10(-5) M]. Ni2+, which has ROC- and VOC-blo cking actions, also abolished nifedipine-insensitive contractions indu ced by ACh. When Ca2+ was replaced with Ba2+, the contraction induced by ACh was blocked by nifedipine. Also, under these conditions, ACh di d not increase the KCl maximum contraction. These data are consistent with there being distinct ROC and VOC influx pathways in guinea pig tr achea and with ROCs playing a significant role in smooth muscle contra ction.