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.