Tetrodotoxin‐sensitive, K⁺‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca²⁺‐entry blocking drugs, Ca²⁺‐free solution and after polyamine exposure

Abstract

1 We have previously observed a paradoxical relaxant effect of K+ on guinea-pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry ofextracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+-entry blocking drugs and in the presence of Ca2+-free solution. 3 A relaxation in response to K+ was also observed in Ca2+-free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain. 4 Tetraethylammonium (30mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. 5 Tetrodotoxin (10-6 M) (TTX) blocked 65% of the K+-induced relaxation in the presence of nifedipine and 100% of K+-induced relaxation either in a Ca2+-free solution or after polyamine exposure. TTX was without effect on TEA-induced relaxation after Ca2+-entry blocking drugs.6 Atropine (10-6 M) or hexamethonium (10-6 M) did not affect K+-induced relaxation after polyamine exposure. 7 The concentration-response curve for K+-induced contraction in normal modified Krebs-Henseleit solution was shifted to the left by TTX. 8 It is concluded: (a) K+ has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca2+-entry blocking drugs, Ca2+-free solution or polyamine exposure; the indirect effect is non-adrenergic, non-cholinergic and not via ganglionic transmission; (b) the TEAinduced relaxation and a component of the K+ -induced relaxation after Ca2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca2+ antagonists.

Increased Ornithine-Derived Polyamines Cause Airway Hyperresponsiveness in a Mouse Model of Asthma

“…However, the few studies in airway physiology have revealed contrasting results. Chideckel and colleagues (32,33) found that spermidine and spermine induced transient relaxation of guinea pig tracheal smooth muscle, and that subsequent exposures resulted in diminished responses, suggesting tachyphylaxis and possibly neurogenic mechanisms. In contrast, Bueb and colleagues (34) demonstrated contractile effects of spermidine and spermine on epithelial-denuded rat tracheal segments.…”

Atropine‐resistant relaxation induced by high K+ in iris dilator muscle of the rat and pig

“…It has been postulated that high K+-induced relaxation in guinea-pig trachea is secondary to release of a non-adrenergic, non-cholinergic inhibitory transmitter(s) (Chideckel et al, 1986). The release by high K+ is sensitive to TTX in that preparation.…”