Peptide receptors in the airways

Abstract

Two categories of peptides exert opposing effects on the isolated guinea pig trachea. Neurokinins (substance P [SP] and congeners) provoke contraction, and kinins (bradykinin) provoke relaxation. Both peptide categories promote the release of relaxing prostaglandins that oppose the contractions induced by neurokinins and mediate entirely the relaxations by the kinins. Receptors for neurokinins have been characterized by comparing the effects of a variety of agonists (naturally occurring or synthetic peptides) in the guinea pig trachea and in other selective preparations. It has been found that the guinea pig trachea contains receptors for neurokinin A (NKA) and for substance P. This has been demonstrated by showing that selective activators of the neurokinin A receptor type are potent stimulants of contraction, and that selective stimulants of the receptors for SP are also active contractile agonists. The order of potency for the neurokinins is NKA greater than NKB greater than SP. The relaxations of guinea pig trachea provoked by bradykinin is not due to the activation of B1 or B2 receptors since it is not modified by specific B1 or B2 antagonists. It is suggested that bradykinin may promote the release of prostaglandins either through a third receptor or by an unknown mechanism. These studies show that the isolated guinea pig trachea is a complex preparation, composed of various tissues and containing different types of neurokinin receptors. The preparation also contains endogenous active agents (e.g., prostaglandins) that are released by the peptides and that may modify or partially or entirely mediate the biologic effects of peptides.