Relaxation and Ca-spike suppression in circular and longitudinal muscles of hog bile duct ampulla by CCK-C-terminal peptides.
The mechanisms by which cholecystokinin (CCK)-C-terminal peptides relax biliary smooth muscles were investigated using circular and longitudinal muscles of hog bile duct ampulla. In normal Tyrode's solution the concentration-contraction curves for acetylcholine (ACh) were in a higher range in circular muscle than in longitudinal muscle. In K+-depolarized muscles the concentration-contraction curves for Ca2+ were in a lower range in circular than in longitudinal muscle. When the Ca2+ concentration in Tyrode's solution was decreased, circular muscle showed concentration-dependent relaxation of normal tone from 1.8 mM to zero calcium, but longitudinal muscle did not show any relaxation. Concentrations of CCK-4, CCK-6 and CCK-7 producing 50% relaxation of normal tone in circular muscles were 19 microM, and 53 nM, respectively; concentrations producing 50% inhibition of ACh-induced contraction in longitudinal muscle were 20, 13 and 47 microM, respectively. The effects of calcium removal on the membrane potential were hyperpolarization in circular muscle but depolarization in longitudinal muscle, although there was cessation of calcium spikes in both muscles. In longitudinal muscle, CCK-4 suppressed spontaneous spikes and evoked spikes. In circular muscle, CCK-4 did not suppress evoked spikes even in a concentration that caused relaxation and hyperpolarization of the membrane. In conclusion, CCK-C-terminal peptides may induce relaxation of circular muscle, not by direct suppression of calcium influx during the action potential, but by intracellular decrease in Ca2+ levels probably arising from increased calcium uptake into the sarcoplasmic reticulum or the plasma membrane. On the other hand, the peptides do not induce relaxation of longitudinal muscle, but suppress only the calcium influx (resulting in cessation of spontaneous contraction). Therefore, CCK-4 may cause a relaxation of normal tone in circular muscle, and an inhibition in the spontaneous contraction, induced by some transmitters, of longitudinal muscle.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013552:Swine
D010446:Peptide Fragments; D002766:Cholecystokinin; D000109:Acetylcholine; D002118:Calcium