The effect of substance P and related peptides on the guinea-pig lung strip.
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 trhe 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 ethylenediaminetetra-acetic 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 X 10(-6) M +/- 4 X 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 X 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).
D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004600:Eledoisin / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010803:Physalaemin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*
D007705:Kinins; D010803:Physalaemin; D013373:Substance P; D002744:Chlorpheniramine; D004600:Eledoisin; D006632:Histamine