The broad objectives of this proposal are to investigate the neurohormonal mechanisms involved in the regulation of the sphincter of Oddi (SO) and gallbladder (GB) motor function and in the physiological interaction between the duodenum and the biliary tract. These studies will be performed in vitro in the muscle bath and in vivo in an isolated duodenal-biliary tract preparation in cats. SO, GB, and duodenal motor function will be determined by measuring mechanical and myoelectrical activity. Our major areas of interest are: 1) analysis of the myoelectrical patterns during basal and stimulated states to determine the extent of electro-mechanical coupling and dissociation and their effects on SO flow rates; 2) pharmacological characterization of receptors of duodenal hormones and neurotransmitters which may participate in the physiological control of the basal or stimulated biliary tract motor function; 3) we will extend our studies of the nature of the intrinsic neural pathways and demonstrate the extrinsic innervation of the biliary tract in order to make possible the study of reflex mechanisms between the duodenum and the biliary tract; 4) we will investigate neurohormonal relationships to define the nature of the interaction between duodenal hormones (CCK, motilin) and the vagus and sympathetic nerves. These studies will permit us to examine possible types of interaction, that is, of potentiation or antagonism which will increase our understanding of what is a physiological stimulus and to develop models of biliary dysfunction; and 5) we will pursue these studies further by examining these neurohormonal relationships under physiological conditions by stimulating the release of endogenous duodenal hormones and/or the activation of reflexes.
