1. Interaction of Neuropeptides on Acetylcholing (ACh) Release: The neuropeptides to be examined include: mammalian bombesin, cholecystokininoctapeptide (CCK-OP), substance P (SP) and vasoactive intestinal peptide (VIP). Two different peptides will be used in combination in each of the experiments and the release of ACh from the myenteric plexus-longitudinal muscle strips will be measured by radiochemical and radioenzymatic methods. 2. Localizaiton of the action of Neuropeptides on Cholinergic Neurons: Neuropeptides listed in #1 will be examined on their ability to modulate ACh release from the isolated myenteric synaptic terminals (synaptosomes). Calcium dependence and requirement for depolarization (activation of Na+ channels) for peptide action will be examined. 3. Characterization of Opiate Receptors on Cholinergic Neurons: Receptors for opioid pepitides (enkephalins and endorphins) will be characterized in terms of the inhibition of ACh release from myenteric plexus neurons, both on basal and on peptide-induced ACh release. Specific blockers will be employed to determine the receptor subtype involved. 4. Mechanism of Release of Gut Neuropeptides: Specific release of neuropeptides in response to depolarizing agents will be examined, using a combined perfusion-chromatography method. ACh, ATP, serotonin and neuropeptides will also be used to elicit release. Quantitation of released peptides will be by RIA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026860-06
Application #
3228071
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Southern Illinois University Carbondale
Department
Type
Schools of Medicine
DUNS #
939007555
City
Carbondale
State
IL
Country
United States
Zip Code
62901
Yau, W M; Mandel, K G; Dorsett, J A et al. (1992) Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus. Am J Physiol 263:G659-64
Yau, W M; Bowen, D J; Youther, M L (1991) Evidence for an involvement of eicosanoids in neurokinin3-receptor mediated acetylcholine release from myenteric neurons. Neurosci Lett 129:259-61
Yau, W M (1990) Mode of stimulation of gallbladder contraction by substance K. Am J Physiol 259:G838-41
Yau, W M; Dorsett, J A; Youther, M L (1990) Modulation of submucosal cholinergic neurons by 5-hydroxytryptamine and neuropeptides. Am J Physiol 259:G1019-24