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Abstract

Effects of indomethacin on neural and myogenic components in equine airway smooth muscle.

K K Gill and E A Kroeger
Journal of Pharmacology and Experimental Therapeutics January 1990, 252 (1) 358-364;
K K Gill
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E A Kroeger
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Abstract

Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally antagonistic CO and lipoxygenase (LO) metabolites. The present studies were designed to assess the relative contributions of altered arachidonic acid metabolism on those respective elements. The utility of the model, in terms of distinguishing neural and myogenic components, was assessed by examining the effects of the muscarinic antagonist atropine (ATR) and the neurotoxin tetrodotoxin (TTX) on the stimulus-response (SR) relationship. The observations that TTX and ATR produced similar rightward (but not downward) shifts of the SR curve and that D-600 inhibited the TTX-insensitive responses are consistent with a selective activation of the muscle by the nerves at lower voltages and a direct stimulation of the muscle at higher voltages. INDO potentiated both the neural and myogenic components of the SR curve, effects which were sensitive to ATR and 5,8,11,14-eicosatetraynoic acid, an inhibitor of LO, and reversed by PGE2. The finding that PGE2 at low doses (10(-8) M) inhibited responses at lower voltages and that at higher concentration (10(-7) M) it shifted the SR curve right and downward suggested that neurotransmitter release is more sensitive to PGE2 inhibition than is muscle response.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 252, Issue 1
1 Jan 1990
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Abstract

Effects of indomethacin on neural and myogenic components in equine airway smooth muscle.

K K Gill and E A Kroeger
Journal of Pharmacology and Experimental Therapeutics January 1, 1990, 252 (1) 358-364;

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Abstract

Effects of indomethacin on neural and myogenic components in equine airway smooth muscle.

K K Gill and E A Kroeger
Journal of Pharmacology and Experimental Therapeutics January 1, 1990, 252 (1) 358-364;
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