The calcium channel agonist BAY K8644 enhances the responsiveness of human airway muscle to KCl and histamine but not to carbachol.
The role of calcium channel antagonists in asthma remains controversial. A new compound BAY K8644 is an agonist at the calcium voltage-dependent channel (VDC). Therefore, we studied the effect of BAY K8644 on contraction to KCl, histamine, and carbachol in human bronchus in vitro to assess the role of the VDC in this tissue. Cumulative concentration response curves were obtained to the agonists in bronchial spiral strips in the absence and in the presence of BAY K8644. Contractile responses to histamine were significantly (p less than 0.05) enhanced by BAY K8644 (10(-6) M) at concentrations between 10(-7) M and 3 X 10(-6) M and there was a significant decrease in the histamine EC50 (the concentration producing half the maximal response). Responses to low concentrations of KCl (10(-4) M to 3 X 10(-3) M) were also potentiated. BAY K8644 did not affect carbachol-induced contractions. We conclude that calcium influx through VDC occurs in response to KCl and histamine but not to carbachol. Such findings could explain the variability in efficacy of calcium channel antagonists in inhibiting various forms of bronchospasm.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D002217:Carbachol / Q000494:pharmacology*; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006632:Histamine; D002217:Carbachol; D002118:Calcium