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P Mike

Publications and source records attributed to P Mike.

4 recordsLinked to original sources
PubMed1987

The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species.

1. The Na+,K+-pump has been implicated in animal models of airway hyperreactivity. We examined the effects of inhibiting the Na+,K+-pump and Na+,Ca2+-exchange on isometric tone of isolated trachealis from humans and other species. 2. In preparations from 5 out of 9 humans, strong spontaneous contractions (36-48 h-1; up to 1.8 g) developed within 25 min. 3. Ouabain (10(-7)-10(-5) M) caused an immediate and sustained contraction. This response was not blocked by atropine, diphenhydramine, or cimetidine. 4. Contractions were also elicited when the normal physiological solution was changed to a K+-free solution, a procedure which inhibits the Na+,K+-pump, and in reduced (15 mM) Na+ solution, which inhibits Na+,Ca2+ exchange. 5. In preparations of dog and guinea-pig isolated trachea, ouabain (10(-5) M) caused a multiphasic response; in the rabbit, ouabain was without effect. K+-free solution was without effect in the dog preparations and produced relaxation of the guinea-pig trachea. Guinea-pig tracheae responded to a low Na+ solution with a strong contraction. 6. Our findings indicate that: (a) human airway smooth muscle may be a spontaneously contracting muscle, at least in vitro, (b) a prolonged contraction to ouabain is unique for the human airway smooth muscle among the animals tested, as is the contraction in a K+-free medium, and (c) the contractile response does not involve acetylcholine or histamine release, but may involve a Na+,Ca2+-exchange mechanism. These results suggest that the level of Na+,K+-pump activity could play a role in determining the degree of bronchomotor tone in humans.

Adult↗
PubMed1986

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.

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 of extracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+-entry blocking drugs and in the presence of Ca2+-free solution. In the presence of nifedipine (10(-5) M), verapamil (10(-5) M) or diltiazem (10(-5) M), K+ (30 mM) induced relaxation of the trachealis muscle. The relaxation to K+ was not blocked by ouabain (10(-6) M), propranolol (10(-6) M), or indomethacin (10(-6) M). 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. Tetraethylammonium (30 mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. 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. Atropine (10(-6) M) or hexamethonium (10(-6) M) did not affect K+-induced relaxation after polyamine exposure. 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.

Animals↗
PubMed1985

Polyamines and putreanine relax respiratory tract smooth muscle in the guinea-pig.

Spermidine, spermine, and putreanine, a metabolite of spermidine, caused transient relaxation of the isolated guinea-pig trachealis. The spermidine effect was not blocked by ouabain, propranolol or indomethacin. Spermidine treatment was shown to desensitize the tissue to subsequent additions of spermidine. After exposure to spermidine and repeated washes with spermidine-free solution, trachealis responded to KCl (30 mM) with a paradoxical relaxation. This relaxation was not blocked by propranolol, ouabain or indomethacin.

Amino Acids, Diamino↗