Abstract

This program project proposal continues to be focused on determination of the sites and mechanisms of action of volatile anesthetics. The current applications proposes four research projects and three cores. Three of the projects continue studies begun by investigators in the previous funding period, and one investigator is new to the program project. The projects are interrelated by the application of a common test panel of compounds of standard anesthetic potency which includes non-immobilizer and translational compounds that were used in the previous funding period. A new feature is the introduction of mutagenesis of putative anesthetic active sites on membrane receptors and studies utilizing transgenic mouse technology. The program will continue to have biannual meetings involving the participant investigators and a number of consultants and advisory board members.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
3P01GM047818-07S1
Application #
6227420
Study Section
Special Emphasis Panel (ZGM1-PS-2 (01))
Program Officer
Cole, Alison E
Project Start
1994-08-01
Project End
2004-07-31
Budget Start
2001-03-01
Budget End
2001-07-31
Support Year
7
Fiscal Year
2001
Total Cost
$73,163
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Cai, Xiaoyun; Huang, Huizhen; Kuzirian, Marissa S et al. (2016) Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling. Genesis 54:29-37
Zarnowska, E D; Rodgers, F C; Oh, I et al. (2015) Etomidate blocks LTP and impairs learning but does not enhance tonic inhibition in mice carrying the N265M point mutation in the beta3 subunit of the GABA(A) receptor. Neuropharmacology 93:171-178
Burkat, Paul M; Lor, Chong; Perouansky, Misha et al. (2014) Enhancement of ?5-containing ?-aminobutyric acid type A receptors by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) is abolished by the ?3(N265M) mutation. Anesth Analg 119:1277-84
Iyer, Sangeetha V; Chandra, Dave; Homanics, Gregg E (2014) GABAA-R ?4 subunits are required for the low dose locomotor stimulatory effect of alphaxalone, but not for several other behavioral responses to alphaxalone, etomidate or propofol. Neurochem Res 39:1048-56
Blednov, Yuri A; Benavidez, Jill M; Homanics, Gregg E et al. (2012) Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor ?1 subunit. J Pharmacol Exp Ther 340:317-29
Borghese, Cecilia M; Blednov, Yuri A; Quan, Yu et al. (2012) Characterization of two mutations, M287L and Q266I, in the ?1 glycine receptor subunit that modify sensitivity to alcohols. J Pharmacol Exp Ther 340:304-16
Pearce, R A; Duscher, P; Van Dyke, K et al. (2012) Isoflurane impairs odour discrimination learning in rats: differential effects on short- and long-term memory. Br J Anaesth 108:630-7
Werner, D F; Swihart, A; Rau, V et al. (2011) Inhaled anesthetic responses of recombinant receptors and knockin mice harboring ?2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J Pharmacol Exp Ther 336:134-44
Chang, Ki-Young; Park, Young-Gyun; Park, Hye-Yeon et al. (2011) Lack of CaV3.1 channels causes severe motor coordination defects and an age-dependent cerebellar atrophy in a genetic model of essential tremor. Biochem Biophys Res Commun 410:19-23
Harris, R A; Osterndorff-Kahanek, E; Ponomarev, I et al. (2011) Testing the silence of mutations: Transcriptomic and behavioral studies of GABA(A) receptor ýý1 and ýý2 subunit knock-in mice. Neurosci Lett 488:31-5

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