Despite being a classic target for the gastrointestinal peptide hormone, cholecystokinin (CCK), the gallbladder CCK receptor is not well characterized. Pharmacological studies of small species suggest that CCK action can be mediated by direct myogenic or by both myogenic and neurogenic receptors. To prepare for the biochemical characterization of a gallbladder CCK receptor and to define the subtype of the receptor being studied, we have performed autoradiographic localization and pharmacological characterization of CCK receptors on bovine gallbladder. Autoradiography demonstrated high-affinity specific CCK-binding sites only on the muscularis. CCK-8 stimulated tonic contraction of longitudinal strips of gallbladder muscularis in a concentration-dependent manner, with an ED50 of 0.2 nM. Antagonism at the cholinergic receptor with 1 μM atropine or axonal transmission with 1 μM tetrodotoxin did not modify CCK-induced contraction, supporting a direct myogenic effect of this hormone. Optimal electrical field stimulation (10 V, 10 Hz, 500 μs) to elicit a neuronal response resulted in muscle strip relaxation, which was abolished with adrenergic blockade (1 μM phentolamine, 1 μM propranolol). Although acetylcholine administration stimulated contraction, electrical field stimulation did not, even in the presence of phentolamine, propranolol, and/or CCK. Thus, in bovine gallbladder muscularis, there is evidence for a functional CCK receptor only on smooth muscle cells. Demonstration of a single, high-affinity specific CCK-binding site on an enriched plasma membrane preparation of bovine gallbladder muscularis is consistent with this representing a myogenic CCK receptor.
|Original language||English (US)|
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|State||Published - 1988|