The effect of substance P and related peptides on the guinea-pig lung strip

Abstract

Substance P is present in sensory nerves in the lung and we report here its actions on the lung strip. Substance P was shown to produce rapid, small contractions of the lung strip at doses from 10⁻⁹ to 10⁻⁵ M, and there was no apparent dose-response relationship. In the presence of a mixture of three inhibitors of substance P breakdown: bacitracin, 1,4-dithio-l-threitol and ethylenediaminetetraacetic acid all at 10⁻⁴ M, the responses to substance P were greatly increased and dose-response curves could be established. The concentrations producing half maximal effect in the presence of these inhibitors were 6×10⁻⁶ M ± 4×10⁻⁶ M. The inhibitors of substance P breakdown were found to have no effect on the histamine dose-response curve: any small shifts obtained were not significant.

Chlorpheniramine 10⁻⁶ M and 10⁻⁵ M shifted the histamine dose-response curve to the right producing dose ratios of 100 and 900 respectively. At these doses chlorpheniramine had no effect on the dose-response curve to substance P. A dose of substance P not itself producing a response (5×10⁻⁸ M) caused an increase in the size of the responses to histamine. The histamine dose-response curve was shifted to the left in the presence of substance P producing an average dose ratio of 1.4±0.2. In the presence of the peptidase inhibitors, dose-response curves have also been produced for physalaemin (10⁻⁷–10⁻⁵ M) and eledoisin (10⁻⁷–10⁻⁵ M).