Contraction of guinea pig lung by synthetic oligopeptides related to human C3a.
Complement-derived human C3a is a 77 residue protein whose biological activities include the contraction of guinea pig ileum and parenchymal lung strips. The C3a molecule is active at submicromolar concentrations and the spasmogenic activities are absolutely dependent on a carboxy-terminal arginyl residue. Studies with synthetic peptide analogues of C3a have localized the active site for all spasmogenic functions at the carboxy-terminal portion of the native molecule. Studies reported here demonstrate that the spasmogenic action of C3a on guinea pig parenchymal lung tissue is mimicked by synthetic peptides based on the carboxy-terminal sequence of C3a. Synthetic peptides with sequences corresponding to the 5, 8, 13 and 21 carboxy-terminal residues of C3a all possess spasmogenic activity on lung tissue. Molar activities of the synthetic peptides relative to that of C3a increase as the length of the peptide increases. The activity of the pentapeptide C3a 73-77 is only 0.5% that of C3a, while those of C3a 70-77 and C3a 65-77 are 3.8 and 7.8%, respectively. A 21 residue peptide, C3a 57-77, exhibits activity equivalent to native C3a. The synthetic peptides, unlike C3a, fail to produce tachyphylaxis. We compared C3a reactivity of guinea pig parenchymal lung strips with those of the synthetic C3a peptides in the presence of various inhibitor combinations. Responses of lung strips to C3a or the C3a peptides were not significantly inhibited by the antihistamine pyrilamine. However, lung responses to synthetic C3a peptides, like those to C3a, were inhibited by indomethacin. Complete inhibition of responses to C3a or the synthetic C3a peptides was produced in the presence of indomethacin, FPL55712 and pyrilamine.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D003176:Complement C3 / Q000494:pharmacology*; D015926:Complement C3a; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors; D013618:Tachyphylaxis / Q000187:drug effects
D002867:Chromones; D003176:Complement C3; D009842:Oligopeptides; D013189:SRS-A; D015926:Complement C3a; C006312:FPL 55712; D011738:Pyrilamine; D000109:Acetylcholine; D007213:Indomethacin