RECEPTOR PHARMACY AND PHYSIOLOGY OF GUT PEPTIDES

Project: Research project

Description

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.
StatusFinished
Effective start/end date9/1/846/30/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Tachykinin Receptors
Reflex
Jejunoileal Bypass
Peptides
Peptide Receptors
Ileum
Vagotomy
Substance P
Autoradiography
Colon
Cats
Intestines
Gastrointestinal Tract
Muscles
Morbidity
Membranes
Uterine Myomectomy
Neurotransmitter Agents
Tachyphylaxis
In Vitro Techniques