Abstract

The objective of our research is to determine the role of neuropeptides in the regulation of neuroendocrine secretion and smooth muscle activity in the gut. Initial work on a prototypical neuropeptide, VIP, will now be extended to the major neuropeptides of the myenteric and submucosal plexuses: somatostatin, CCK-OP, methionine- and leucine-enkephalin, substance P and bombesin. Smooth muscle cells will be isolated from the longitudinal and circular smooth muscle of the intestine of the guinea pig and examined for the presence of specific receptors to neuropeptides. Receptors will be characterized in terms of mechnical activity, messenger systems (Ca++ fluxes and cAMP accumulation) and binding sites (radioiodinated ligands). The release of neuropeptides will be examined in muscle strips, vascularly perfused intestine and in isolated segments of fresh and cultured neural plexus. The regulation of an endocrine peptide (gastrin) by a paracrine peptide (somatostatin) and by cholinergic and peptidergic intramural neurons will be investigated in the vascularly perfused stomach of the rat.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM015564-14
Application #
3150962
Study Section
(SSS)
Project Start
1979-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
14
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Schubert, M L; Saffouri, B; Makhlouf, G M (1988) Identical patterns of somatostatin secretion from isolated antrum and fundus of rat stomach. Am J Physiol 254:G20-4
Grider, J R; Makhlouf, G M (1987) Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut. Gastroenterology 92:175-80
Grider, J R; Makhlouf, G M (1987) Suppression of inhibitory neural input to colonic circular muscle by opioid peptides. J Pharmacol Exp Ther 243:205-10
Schubert, M L; Edwards, N F; Arimura, A et al. (1987) Paracrine regulation of gastric acid secretion by fundic somatostatin. Am J Physiol 252:G485-90
Grider, J R; Makhlouf, G M (1987) Prejunctional inhibition of vasoactive intestinal peptide release. Am J Physiol 253:G7-12
Bitar, K N; Bradford, P G; Putney Jr, J W et al. (1986) Stoichiometry of contraction and Ca2+ mobilization by inositol 1,4,5-trisphosphate in isolated gastric smooth muscle cells. J Biol Chem 261:16591-6
Grider, J R; Makhlouf, G M (1986) Colonic peristaltic reflex: identification of vasoactive intestinal peptide as mediator of descending relaxation. Am J Physiol 251:G40-5
Bitar, K N; Makhlouf, G M (1986) Measurement of function in isolated single smooth muscle cells. Am J Physiol 250:G357-60
Bitar, K N; Bradford, P; Putney Jr, J W et al. (1986) Cytosolic calcium during contraction of isolated mammalian gastric muscle cells. Science 232:1143-5
Loewe, C J; Grider, J R; Gardiner, J et al. (1985) Selective inhibition of pentagastrin- and cholecystokinin-stimulated exocrine secretion by proglumide. Gastroenterology 89:746-51

Showing the most recent 10 out of 14 publications