RECEPTOR PHARMACY AND PHYSIOLOGY OF GUT PEPTIDES

这个应用程序的目的是确定分布，密度和

The aim of this application is to determine the distribution, density and properties of tachykinin receptors in the intestine of the rat and cat and to determine the relationship between receptor properties and physiologic function and to examine the effect of intraluminal contents and extrinsic innervation on the receptor distribution and properties. Tachykinin receptors will be examined in detail using several techniques: a) quantitative autoradiography to determine the distribution and density of receptors in different areas of the gastrointestinal tract both in the normal state and following manipulation studies; b) emulsion autoradiography which, as a result of its higher resolution, will allow correlation of specific binding with microscopic structures; and c) binding studies using purified membrane preparations to allow the biochemical determination of whether the receptors are located on muscle membrane of synaptasomes. This distinction is important to explain discrepancies in the literature. The effect of intraluminal contents on tachykinin receptor distribution and density will be examined using an intestinal bypass model. The effects of extrinsic innervation will be examined using an intestinal bypass model. The effects of extrinsic innervation will be examined by the use of chronic vagotomy and chronic sympathectomy models. In each case, autoradiographic findings will be correlated with functional studies, as assessed by in vitro muscle bath preparations in the rat and cat and in vivo studies of the myoelectrical and contractile responses of the myoelectrical and contractile responses of the distal ileum, ileocecal sphincter (ICS) and colon model in the cat; which shows a contractile reflex at the ICS to distal distension and an inhibitory reflex at the ICS to proximal distention. Substance P has been shown to mediate the contractile response. A study of the relationship between peptide distribution, receptor distribution and physiological effect will allow a determination of the significance of receptor properties in the control of intestinal motor function. Such a determination has implications in the study of intestinal motor diseases in man, in most of which no anatomic abnormality has been described. It will indicate whether studies of receptor function may provide insight into the pathophysiology of these poorly defined disorders, which result in significant morbidity in the United States.