Effects of two Ca2+ modulators in normal and albumin-sensitized guinea-pig trachea.
The voltage-dependent Ca2+ channel blocker, verapamil, and the calmodulin antagonist, trifluoperazine, each reduced resting tone and attenuated constriction induced by acetylcholine or vagal stimulation in normal guinea-pig trachea. Attenuation of vagal responses involved both pre- and post-junctional effects on cholinergic neurotransmission. In albumin-sensitized trachea both drugs caused small increases in resting tone. Vagally mediated constrictor responses were resistant to attenuation by verapamil in sensitized trachea. Trifluoperazine was less effective against acetylcholine-induced tone in sensitized, as compared to untreated, trachea. The results indicate that Ca2+ handling is altered in airway smooth muscle in this animal model of bronchial asthma. Abnormal Ca2+ handling, therefore, may underlie the hyperresponsiveness to vagal input exhibited in sensitized trachea and could contribute to the generalised airway hyperreactivity characteristic of asthma.
McCaig
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D
School of Pharmacy, Robert Gordon University, Schoolhill, Aberdeen, Scotland, UK.
De Jonckheere
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000418:Albumins; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007114:Immunization; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology; D014268:Trifluoperazine / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology*
D000418:Albumins; D014268:Trifluoperazine; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium