The objective of this proposal is to characterize the properties of smooth muscle cells isolated from the mammalian gut. We have developed techniques for isolation of muscle cells from the stomach (guinea pig, dog and man) and gallbladder (dog and man) and have devised an image-splitting micrometric technique for the direct measurement of contraction and relaxation. We have also applied techniques for the indirect measurement of muscle cell response in terms of cellular intermediates: intracellular levels of cyclic nucleotides; 45Ca ions efflux and the phosphorylated fraction of myosin light chain (using IEF/SDS electrophoresis).
The specific aims of the proposal are: 1) to identify and characterize smooth muscle receptors for gut peptides; these are known to be present in nerve fibers of the submucous and myenteric plexuses of the gut and are thought to play a physiological role as neurotransmitters or neuromodulators in the control of smooth muscle activity; the most likely candidates are VIP, the opioid peptides (met- and leu-enkephalin), substance P and bombesin. 2) To define the contractile response to peptides by measurement of 45Ca ions efflux and the phosphorylated fraction of myosin light chain, and 3) To define the role of cyclic AMP in smooth muscle relaxation induced by VIP and its homologues and test the possibility that ATP (the putative 'purinergic' relaxant neurotransmitter) and VIP interact synergistically to modulate neurally-induced relaxation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028300-08
Application #
3228712
Study Section
(GCN)
Project Start
1984-04-01
Project End
1989-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Mahavadi, Sunila; Nalli, Ancy D; Wang, Hongxia et al. (2018) Regulation of gastric smooth muscle contraction via Ca2+-dependent and Ca2+-independent actin polymerization. PLoS One 13:e0209359
May, Alexander T; Crowe, Molly S; Blakeney, Bryan A et al. (2018) Identification of expression and function of the glucagon-like peptide-1 receptor in colonic smooth muscle. Peptides 112:48-55
Blakeney, Bryan A; Crowe, Molly S; Mahavadi, Sunila et al. (2018) Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway. Dig Dis Sci :
Mahavadi, Sunila; Grider, John R; Murthy, Karnam S (2018) Muscarinic m2 receptor-mediated actin polymerization via PI3 kinase ? and integrin-linked kinase in gastric smooth muscle. Neurogastroenterol Motil :e13495
Parikh, Jay; Zemljic-Harpf, Alice; Fu, Johnny et al. (2017) Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction. J Sex Med 14:1177-1186
Nalli, Ancy D; Wang, Hongxia; Bhattacharya, Sayak et al. (2017) Inhibition of RhoA/Rho kinase pathway and smooth muscle contraction by hydrogen sulfide. Pharmacol Res Perspect 5:
Mahavadi, Sunila; Sriwai, Wimolpak; Manion, Olivia et al. (2017) Diabetes-induced oxidative stress mediates upregulation of RhoA/Rho kinase pathway and hypercontractility of gastric smooth muscle. PLoS One 12:e0178574
Qian, Jie; Mummalaneni, Shobha; Phan, Tam-Hao T et al. (2017) Cyclic-AMP regulates postnatal development of neural and behavioral responses to NaCl in rats. PLoS One 12:e0171335
Nalli, Ancy D; Bhattacharya, Sayak; Wang, Hongxia et al. (2017) Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide. Am J Physiol Gastrointest Liver Physiol 313:G330-G341
Qian, Jie; Mummalaneni, Shobha K; Alkahtani, Reem M et al. (2016) Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells. PLoS One 11:e0166565

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