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Cellular Regulation of Human Proximal stomach Motor Responses
Summary Data Summary
Applicant Perrino, Brian
E-Mail Address bperrino@med.unr.edu
Project Title Cellular Regulation of Human Proximal stomach Motor Responses
CBU ID 14GHSU1397
External SubContract ID 25732-62
Diabetic Complication Gastro-Intestinal (GI)
Funding Program Group Pilot & Feasibility [PF2014]
Abstract Gastric motility defects present as functional dyspepsia or gastroparesis and
often arise as complications of obesity and diabetes. The prevalence of diabetic
gastroparesis is increasing due to the increasing incidence of obesity and type
2 diabetes in the US. The objective of the proposed project is to establish a
better understanding of the cellular basis of human gastric fundus motility to
develop more extensive and focused investigations utilizing NIH R01 and/or P01
levels of support. This study will provide the first evaluation of Ca2+
sensitization mechanisms in human gastric fundus smooth muscles activated by
acetylcholine (ACh) in its physiological role as a neurotransmitter. The
proposed studies will detail the mechanisms by which myofilament sensitivity to
Ca2+ is increased by cholinergic neurotransmission, define approaches that can
further increase Ca2+ sensitivity, and examine the potential role of
interstitial cells of Cajal (ICC) in specifying how the cholinergic signal
increases Ca2+ sensitivity. These studies will have relevance to the clinical
management of diabetic gastroparesis by providing a better understanding of the
mechanism by which the novel cholinesterase inhibitor Acotiamide improves
gastric motility and clinical symptoms in patients with functional dyspepsia or
gastroparesis. The specific aims are:

1.Determine the importance of Ca2+ sensitization mechanisms for gastric fundus
smooth muscle contraction by cholinergic neurotransmission. We will compare Rho
kinase and protein kinase C activation by cholinergic neurotransmission and bath
application of carbachol by measuring MYPT1 and CPI-17 phosphorylation. We will
use the cholinesterase inhibitor neostigmine to define conditions that increase
acetylcholine levels and MYPT1 and CPI-17 phosphorylation, and potentiate the
contractile responses.

2. Evaluate the contribution of loss of ICC function to altered Ca2+
sensitization pathways in human gastric fundus smooth muscles. We will examine
how disrupting the activity of interstitial cells of Cajal with the novel ANO1
inhibitor benzbromarone affects the activation of Ca2+ sensitization pathways in
fundus smooth muscles by cholinergic neurotransmission.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 32382
Supply Total Costs 9430
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 41812
Indirect Costs Proposed 0
Total Costs Proposed 41812
Total Costs Approved 60000
Start Date 10/1/2014
End Date 9/30/2015
IFO Name hart, Charlene
IFO E-Mail Address ospadmin@unr.edu
IACUC/IRB No. 2013-019
IACUC/IRB Institution University of Nevada-Reno
Entity ID No. 188-000024A1
Report Request Date 10/30/2015
T1D NO
TypeCount
Invoices 12
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU139725732-62University of Nevada-Reno7/17/2017$379.72$165.17$544.89-View PDF
  View  14GHSU139725732-62University of Nevada-Reno6/14/2017$5,964.30$2,594.47$8,558.77-View PDF
  View  14GHSU139725732-62University of Nevada-Reno5/18/2016$11,014.57$4,791.34$15,805.91-View PDF
  View  14GHSU139725732-62University of Nevada-Reno4/21/2016$884.90$384.93$1,269.83-View PDF
  View  14GHSU139725732-62University of Nevada-Reno4/21/2015$1,937.01-$1,937.01-View PDF
  View  14GHSU139725732-62University of Nevada-Reno3/9/2016$8,367.17$3,639.72$12,006.89-View PDF
  View  14GHSU139725732-62University of Nevada-Reno2/3/2016$3,046.65-$3,046.65-View PDF
  View  14GHSU139725732-62University of Nevada-Reno12/16/2015$5,255.30-$5,255.30-View PDF
  View  14GHSU139725732-62University of Nevada-Reno11/24/2015$7,242.59-$7,242.59-View PDF
  View  14GHSU139725732-62University of Nevada-Reno10/6/2015$3,216.68-$3,216.68-View PDF
  View  14GHSU139725732-62University of Nevada-Reno10/5/2016$299.24$130.17$429.41-View PDF
  View  14GHSU139725732-62University of Nevada-Reno1/21/2015$686.07-$686.07-View PDF


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