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Stimulation of sodium pump by vasoactive intestinal peptide in guinea‐pig isolated trachea: potential contribution to mechanisms underlying relaxation of smooth muscle
Author(s) -
Morrison Keith J.,
Vanhoutte Paul M.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15438.x
Subject(s) - vasoactive intestinal peptide , ouabain , chemistry , endocrinology , medicine , contraction (grammar) , muscle relaxation , sodium nitroprusside , forskolin , muscle contraction , isoprenaline , stimulation , sodium , biochemistry , biology , nitric oxide , neuropeptide , receptor , organic chemistry
1 Relaxation of airway smooth muscle induced by vasoactive intestinal peptide (VIP) is mediated by adenosine 3′:5′ cyclic monophosphate (cyclic AMP). An interaction between the synthesis of cyclic AMP and enzymic activity of the plasmalemmal sodium pump (Na + ‐K + ‐ATPase) exists in certain isolated cell systems. This study sought to determine the contribution of Na + ‐K + ‐ATPase activity to relaxation of airway smooth muscle evoked by VIP. 2 All experiments were performed on isolated strips of guinea‐pig trachea from which the epithelium had been removed. VIP was a more potent relaxant in tissues that were contracted with carbachol than those contracted with an equi‐effective depolarizing concentration of K + . 3 Ouabain (0.1 μ m ‐10 μ m ) induced contraction of tracheal strips. Contraction to ouabain (5 μ m ) was abolished following incubation of tissues with K + ‐free, or Ca 2+ ‐free (+EGTA, 0.1 mM) physiological solutions. The contractile response to ouabain (5 μ m ) was not influenced significantly by exposure of the tissues to atropine (1 μ m ), phentolamine (5 μ m ) and diphenhydramine (1 μ m ) for 60 min. 4 Tissues were incubated with ouabain (5 μ m ; 60 min) or K + ‐free physiological solution (60 min) to inhibit Na + ‐K + ‐ATPase activity. These procedures reduced relaxation induced by VIP, peptide histidine isoleucine, forskolin, isoprenaline and sodium nitroprusside. 5 Relaxation to VIP was impaired significantly following exposure of tissues to a low Na + solution (30 min) or amiloride (500 μ m ; 30 min). 6 Ouabain‐sensitive uptake of 86 Rb was measured in tracheal strips (devoid of epithelium and cartilage) as an index of Na + ‐K + ‐ATPase activity. VIP (1 μ m ; 2 min) caused a 4.7 fold stimulation of ouabain‐sensitive uptake of 86 Rb. This effect was impaired significantly by low Na + solution. 7 The results suggest that (i) relaxation of tracheal smooth muscle to VIP is sensitive to procedures that inhibit activity of Na + ‐K + ‐ATPase and invoke a role for altered sodium pump function in the mechanisms that underlie cyclic AMP‐dependent relaxation; and (ii) VIP stimulates ouabain‐sensitive uptake of 86 Rb in airway smooth muscle in a Na + ‐dependent manner.