ABSTRACT
We have investigated the role of sensory nerves in regulating airway smooth muscle function in the guinea-pig, marmoset, rabbit and man. Tissue levels of the sensory neuropeptides CGRP and substance P in the airways of the guinea-pig were significantly greater compared with the rabbit and marmoset. The relative order of tissue content was guinea-pig >>> rabbit = marmoset. Marmoset bronchial and tracheal preparations responded weakly to exogenously administered substance P and neurokinin A but contracted to methacholine and demonstrated atropine-sensitive cholinergic responses. In marmoset, rabbit and human airway preparations, capsaicin mediated weak contractile responses to exogenously administered capsaicin. However, high concentrations of capsaicin elicited a relaxation response that was epithelium-independent, cyclo-oxygenase-insensitive, not involving nitric oxide and not dependent on the activation of capsaicin-sensitive afferents. These results suggest that rabbit and marmoset airways respond functionally in a similar way to human airway preparations and maybe more relevant than guinea-pig airways with regard to understanding the role of sensory neuropeptides in airways.
Subject(s)
Neurons, Afferent/physiology , Respiratory System/innervation , Animals , Callithrix , Capsaicin/pharmacology , Electric Stimulation , Guinea Pigs , Humans , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/innervation , Muscle, Smooth/metabolism , Muscle, Smooth/physiology , Neurons, Afferent/metabolism , Neuropeptides/metabolism , Neuropeptides/pharmacology , Parasympathetic Nervous System/drug effects , Parasympathetic Nervous System/physiology , Rabbits , Respiratory System/metabolism , Species SpecificityABSTRACT
The synthesis of alkyl and aryl ureas (II) derived from 5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2.]nonane (I), as well as hydrazides (V), (VI) and (VII) derived from 5,7,7-trimethyl-6-oxa-3-azabicyclo[3.2.2]-nonan-3-amine (IV), is described. A number of theses compounds showed strong hypotensive and bradycardic activities in rats, as well as weak infiltration anesthesia and antiarrhythmic activity in mice. Antiacetylcholine activity in vitro is also reported.
