Roles of Ca2+ influx and intracellular Ca2+ release in agonist-induced contractions in guinea pig trachea.
The contribution of receptor-operated Ca2+ channels (ROCs), voltage-operated Ca2+ channels (VOCs), and intracellular Ca2+ release to contractions 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 ether)-N,N,N',N'-tetraacetic acid (EGTA) (4 x 10(-3) M for 5 min) markedly 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 contractions induced by other agonists. The ROC (and VOC) blocker, SK&F 96365 (10(-5)-10(-4) M), inhibited both KCl-induced contractions and the nifedipine-insensitive component of contractions induced by acetylcholine (ACh), U46619, or leukotriene D4 [half maximal inhibitory concentration (IC50) values 1.7-3.8 x 10(-5) M]. Ni2+, which has ROC- and VOC-blocking actions, also abolished nifedipine-insensitive contractions induced by ACh. When Ca2+ was replaced with Ba2+, the contraction induced by ACh was blocked by nifedipine. Also, under these conditions, ACh did not increase the KCl maximum contraction. These data are consistent with there being distinct ROC and VOC influx pathways in guinea pig trachea and with ROCs playing a significant role in smooth muscle contraction.
Bayer Pharmaceutical Research Department, Stoke Poges, United Kingdom.
N J
NJ
Cuthbert
P J
PJ
Gardiner
K
K
Nash
C T
CT
Poll
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism / Q000502:physiology*
D002121:Calcium Channel Blockers; D007093:Imidazoles; D001464:Barium; D004533:Egtazic Acid; D009532:Nickel; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium