The Quest for the Inhibitory Neurotransmitter in Bovine Tracheal Smooth Muscle

Abstract

SUMMARYThe effect of inhibitory nerve stimulation on the mechanical, membrane potential and membrane conductance responses of isolated bovine tracheal smooth muscle has been studied.Membrane responses were measured in a sucrose-gap apparatus. In order to record inhibitory responses, it was necessary to increase tone in the preparation by applying a drug such as histamine. When tone was raised, repetitive field stimulation of intrinsic nerves caused depolarization and contraction, followed by relaxation and a suppression of histamine-induced slow waves. Hyperpolarization of the membrane was only seen following prolonged nerve stimulation, and there was no change in membrane conductance. The inhibitory effect of nerve stimulation was abolished by tetrodotoxin, but was not abolished by atropine, indomethacin, propranolol, naloxone or the purinergic blockers quinidine and theophylline. It was not satisfactorily mimicked by catecholamines, by y-amino-n-butyric acid (GABA) or by purines.Nerves with catecholamine fluorescence could not be found in the tracheal muscle layer. Neither adrenergic nor purinergic types of nerve terminal could be found in the tracheal muscle layer during ultrastructural examination of over one thousand nerve profiles. Vasoactive intestinal peptide (VIP) caused relaxation of the histamine-contracted tracheal muscle, suppressed the slow wave and caused slight hyperpolarization at higher concentrations, without affecting the membrane conductance. VIP was found in samples of tracheal muscle at a mean concentration of 1-95 ng/g. When the effluent solution flowing past isolated tracheal muscle strips was assayed for VIP, samples collected during inhibitory nerve stimulation had much higher concentrations ofthe peptide than samples collected before stimulation, after stimulation, or during stimulation in the presence of tetrodotoxin (10-6 mol/l). The VIP content of the effluent during control periods was 73-8 pg/ml, and during stimulation was 167 5 pg/ml. It is suggested that VIP might be the non-adrenergic inhibitory neurotransmitter in bovine tracheal smooth muscle.

Electrophysiological and other aspects of the relaxant action of isoprenaline in guinea‐pig isolated trachealis

“…The present experiments have shown that the guineapig trachealis resembles that of the ox (Kirkpatrick, 1981;Cameron et al, 1983) and dog (Suzuki et al, 1976;Ito & Tajima, 1982) in that the inhibitory action of isoprenaline is accompanied by hyperpolarization.…”

“…In the trachealis of the ox and dog the inhibitory It also seems to represent an increase in membrane effects of adrenaline or isoprenaline are associated conductance (presumably to K+) because electrotonic with hyperpolarization of the muscle cells (Suzuki et potentials evoked by the passage of current pulses are al., 1976; Kirkpatrick, 1981;Ito & Tajima, 1982; reduced in amplitude during the hyperpolarization Cameron et al, 1983). This hyperpolarization seems to (Ito & Tajima, 1982;Cameron et al, 1983).…”

Vasoactive intestinal peptide in bovine pulmonary artery: localisation, function and receptor autoradiography

“…Although the neurotransmitters involved in this 'third' nervous system are not yet certain, there is some evidence that neuropeptides may be involved (Barnes, 1984). Non-adrenergic inhibitory nerves have been demonstrated in the lung, particularly in airway smooth muscle (Richardson, 1981) and there is evidence that vasoactive intestinal peptide (VIP) might be a neurotransmitter since VIP has been localised in these nerves by immunocytochemical methods (Dey et al, 1981;Laitinen et al, 1985) and VIP has been found to relax partially airway smooth muscle (Said, 1982;Cameron et al, 1983;Palmer et al, 1985). A NANC inhibitory response has also been 'Author for correspondence at: Department of Clinical Pharmacology,Cardiothoracic Institute,Fulham Road,London SW3 6HP demonstrated in the pulmonary artery of several species (Hamaski et al, 1983b;Frank & Bevan, 1983).…”

Possible role of calcium in neurotransmission to the lower airways.

“…It is in keeping with the general concept of mediator release that calcium channels should be important in this system too but, as far as I know, nobody has demonstrated that peptide release depends upon the presence of calcium and might be inhibited by calcium-antagonists. The most likely candidate for the NAIS bronchodilatory system is vasoactive intestinal polypeptide (VIP) (Cameron et al, 1983) and it would be of con- Of great current interest is the demonstration that stimulation of sensory afferent fibres in the airways (including the nose) can set up local reflexes involving the release of the mediator substance P, which may have a bronchoconstrictor action as well as a secretagogue effect (Lundberg & Saria, 1983;Karlsson & Persson, 1983). Again, the discussion must centre on analogy with other systems.…”