Abstract
The present study was carried out to investigate whether there is the difference between low and high frequencies of vagal stimulation on the functional appearance of M 2 receptors in the rabbit. The animals were anesthetized, artificially ventilated and bilaterally vagotomized. Bilateral vagus nerve stimulation (5 to 30 Hz) for 30 sec caused bronchoconstriction (measured as an increase in R L and a decrease in Cdyn) in a frequency-dependent manner. The bronchoconstriction evoked by ACh injection (1 and 3 μg kg ) was dose-dependent. Although administration of methoctramine (50 and 300 μg kg ), a selective M 2 receptor antagonist, had no significant effect on ACh-induced bronchoconstriction, methoctramine dose-dependently augmented the R L and Cdyn responses to vagal stimulation at 5–15 Hz but did not potentiate bronchoconstrictive responses to the stimulation at 30 Hz. Administration of [D-Pro 2, D-Try 7,9]-SP (0.5 mg kg , a selective tachykinin receptor antagonist) that had no significant effect on the R L and Cdyn responses to vagal stimulation (5–15 Hz) attenuated the bronchoconstrictive response to the stimulation at 30 Hz. Conversely, thiorphan (2 mg kg , a neutral endopeptidase inhibitor) potentiated the bronchoconstriction evoked by vagal stimulation at 30 Hz only. These results suggest that M 2 receptors function as the inhibitory receptors in the bronchoconstrictive response to vagal stimulation at the lower frequencies (5–15 Hz), but that the M 2 receptor antagonism is diminished when vagal stimulation at a higher frequency (30 Hz) results in the release of SP from the lungs.
Published Version
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