ENTERIC PHYSIOLOGY AND FUNCTION OF THE TRANSPLANTED GUT

  • Sarr, Michael Gregory, (PI)

Project: Research project

Description

Transplantation of the upper gut will soon become a clinical
reality and yet, while many studies have addressed the immunologic
phenomena of the transplanted gut, little is known about the
effects on the physiology of enteric function. Study of enteric
physiology of the transplanted gut represents a new field with
clinical and physiologic ramifications. This proposal has two
relevant_and complimentary LONG TERM OBJECTIVES: to determine how
intestinal transplantation alters gastrointestinal physiology and
function; and to elucidate mechanisms of neural and hormonal
control of motility and absorption via study or the denervated
(transplanted) jejunoileum. Using a model of orthotopic
autotransplantation of the entire jejunoileum to avoid con-
founding effects of immune rejection/immunosuppression, Part A of
this proposal expands a previous series of experiments on motility;
Part B addresses neurohormonal control of absorptive physiology.
SPECIFIC AIMS. Part A--Motility: To determine how jejunoileal
transplantation affects mechanisms controlling: 1) neural and
hormonal control of motility patterns of the stomach and small
intestine; 2) jejunoileal regulation of gastroduodenal motility
and 3) gastroduodenal_regulation of jejunoileal motility. Part B-
-Absorption: 1) To characterize temporal changes after jejunoileal
transplantation in specific jejunal and ileal absorptive functions
from the whole gut, and net absorption and transit or water,
electrolytes, and nutrients in transplanted jejunal and ileal loops
in vivo. 2) To focus on mechanisms in vivo studying elective
denervations (vagal, sympathetic, both), and by study temporal
changes after intestinal transplantation in: absorptive response
to specific pharmacologic agents; tissue concentrations of
regulatory endocrine and neurocrine peptides, cAMP, and brush
border enzyme serosal electrodes and perfused intraluminal
manometry catheters to measure motility in vivo by myoelectric and
contractile activity. Absorption and transit will be assessed with
radiolabelled foods and with intestinal perfusion and radiolabelled
markers. Peptides will be evaluated using validated
radioimmunoassays and immunohistochemistry. Morphologic analysis
will use quantitative light microscopic morphometry and scanning
electron microscopy. These experiments are directly relevant and
will be clinically-applicable in understanding motor and absorptive
aspects of the physiology of enteric function after intestinal
transplantation.
StatusFinished
Effective start/end date5/1/895/31/10

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $240,504.00
  • National Institutes of Health: $283,790.00
  • National Institutes of Health: $299,300.00
  • National Institutes of Health: $269,370.00
  • National Institutes of Health: $247,717.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $262,800.00
  • National Institutes of Health: $255,147.00
  • National Institutes of Health
  • National Institutes of Health: $292,266.00
  • National Institutes of Health

Fingerprint

Transplantation
Smooth Muscle
Denervation
Stomach
Peptides
Food
Anatomic Models
varespladib methyl
Microvilli
Immunosuppression
Electrolytes
Isogeneic Transplantation
Water
Perfusion
Biosensing Techniques
Immunohistochemistry
Ileum
Light
Carrier Proteins
Microscopy

ASJC

  • Medicine(all)