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Endothelin differentially affects rat gastric longitudinal and circular smooth muscle
J Fulginiti1, M M Cohen, R S Moreland
1Bockus Research Institute, Graduate Hospital, Philadelphia, Pennsylvania.
Summary
Endothelin-1 (ET-1) causes concentration-dependent contractions in rat forestomach longitudinal smooth muscle, but inhibits fundus circular smooth muscle activity. These distinct gastric smooth muscle responses to ET-1 were investigated.
Area of Science:
- Gastroenterology
- Pharmacology
- Physiology
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor peptide.
- Gastric smooth muscle exhibits distinct tonic and phasic activities.
- The role of ET-1 in gastric smooth muscle function requires further elucidation.
Purpose of the Study:
- To investigate the effects of endothelin-1 (ET-1) on two distinct types of rat gastric smooth muscle.
- To characterize the contractile and inhibitory responses of longitudinal and circular gastric smooth muscle to ET-1.
Main Methods:
- Cumulative addition of ET-1 to isolated rat forestomach longitudinal smooth muscle and fundus circular smooth muscle preparations.
- Measurement of muscle contraction and spontaneous phasic activity.
- Use of pharmacological agents including nifedipine, calcium-free solutions, and inhibitors of various signaling pathways.
Main Results:
- ET-1 induced concentration-dependent contractions in longitudinal smooth muscle, dependent on extracellular calcium.
- ET-1 potently inhibited spontaneous and carbachol-stimulated phasic activity in circular smooth muscle.
- The inhibitory effects of ET-1 on circular smooth muscle were not reversed by inhibitors of arachidonic acid products, nitric oxide, or neural pathways.
Conclusions:
- ET-1 exerts differential effects on rat gastric smooth muscle, causing contraction in longitudinal muscle and inhibition in circular muscle.
- The mechanisms underlying ET-1's actions involve calcium-dependent pathways in longitudinal muscle and distinct, non-neural, non-arachidonic acid pathways in circular muscle.