The Effect of Cocaine on the Responses of the Differently Innervated Laryngeal and Bronchial Ends of the Guinea Pig Trachea in Vitro to Clinically used Bronchodilators

Abstract

Fluorescent histochemical studies indicate that guinea pig tracheal smooth muscle has sparse adrenergic innervation with the greatest nerve density being located at the laryngeal end. In the present study, log dose–response lines were obtained for dl-isoprenaline (ISO), l-adrenaline (ADR), l-noradrenaline (NOR), salbutamol (SALB), and orciprenaline on isolated tracheal chains prepared from both the laryngeal (L) and bronchial (B) ends of the trachea. Responses were obtained in the absence and presence of the Uptake1 blocker, cocaine (0.67 and 6.7 μM) which markedly potentiated responses to NOR and ADR but failed to significantly alter responses to ISO and SALB on L preparations. The degree of potentiation obtained on B preparations was significantly less for NOR and ADR and was not significant for the other agents. In addition, experiments were carried out on tracheal chains which developed their normal tone in the absence of carbachol, and also on preparations obtained from 6-hydroxydopamine treated animals. The present findings, based on selective potentiation of NOR and ADR, support evidence that the degree of adrenergic innervation to the guinea pig trachea is greater at the laryngeal end, and the results obtained with cocaine strengthen the argument that it has a pre-synaptic site of action.