Pharmacological Effects of Peptides on Tracheal Smooth Muscle

Abstract

Peptide and non-peptide agents were tested for their stimulatory or inhibitory effects on circular strips of guinea pig isolated tracheae. Substance P, eledoisin, physalaemin, neurotensin, angiotensin, histamine and carbachol were found to contract, while noradrena-line, dopamine, bradykinin, nucleotides (AMP, ADP, ATP) and prostaglandins (PGE_1; PGE₂, PGA₂) induced concentration-dependent relaxations of tracheae contracted with substance P or carbachol. Indomethacin (2.8 × 10^–6M) significantly potentiated the effect of substance P and blocked that of bradykinin. The contractions to substance P of tissues treated with indomethacin were not modified by atropine, methysergide, diphenhydramine, cimetidine, pro-pranolol, phentolamine, [Leu⁸]-AT₁₁, [Leu⁸]-des-Arg⁹-bradykinin, naloxone and baclofen. The order of potency of C-terminal fragments of substance P was: hexa(6–11) > hepta(5–11) > substance P > = octa(4–11). It is concluded that the guinea pig isolated trachea is a pharmacological preparation sensitive to numerous agents and useful for studying structure-activity relationship and the mechanism of cellular action of several peptides, particularly substance P.