Abstract

Ethanol inhibits the release of vasopressin from the neural lobe of the rat. The proposed work will use a combined biochemical and electrophysiological approach to determine the mechanisms by which alcohol affects this release. Experiments will be performed on the intact neural lobe, and on a recently-developed preparation of pure neural lobe nerve terminal (neurosecretosomes), in which alcohol produces a similar inhibition of release. If the membrane of the secretosomes is permeabilized with digitonin, ethanol no longer has an effect, suggesting that membrane channels are a target of ethanol. The neurosecretosome is a perfect subject for patch clamp analysis. In the proposed research, patch clamp techniques will be used to correlate EtOH's actions on membrane channels with its effects on release of hormone. In the final pat of the proposal, we will use the electrophysiological and biochemical techniques describe above to examine EtOH's effects on channel activity and hormone release from the NL and from terminals isolated from the NL, in rats selectively greed for particular aspects of alcohol responsivity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA008003-01
Application #
3111893
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1989-01-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
01545

  Publications

Velázquez-Marrero, Cristina; Ortiz-Miranda, Sonia; Marrero, Héctor G et al. (2014) ?-Opioid inhibition of Ca2+ currents and secretion in isolated terminals of the neurohypophysis occurs via ryanodine-sensitive Ca2+ stores. J Neurosci 34:3733-42
Pietrzykowski, Andrzej Z; Ortiz-Miranda, Sonia; Knott, Thomas K et al. (2013) Molecular tolerance of voltage-gated calcium channels is evident after short exposures to alcohol in vasopressin-releasing nerve terminals. Alcohol Clin Exp Res 37:933-40
Velázquez-Marrero, Cristina; Wynne, Patricia; Bernardo, Alexandra et al. (2011) The relationship between duration of initial alcohol exposure and persistence of molecular tolerance is markedly nonlinear. J Neurosci 31:2436-46
Ortiz-Miranda, Sonia I; Dayanithi, Govindan; Velázquez-Marrero, Cristina et al. (2010) Differential modulation of N-type calcium channels by micro-opioid receptors in oxytocinergic versus vasopressinergic neurohypophysial terminals. J Cell Physiol 225:276-88
Feinberg-Zadek, Paula L; Martin, Gilles; Treistman, Steven N (2008) BK channel subunit composition modulates molecular tolerance to ethanol. Alcohol Clin Exp Res 32:1207-16
Martin, Gilles E; Hendrickson, Linzy M; Penta, Krista L et al. (2008) Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol. Proc Natl Acad Sci U S A 105:17543-8
Pietrzykowski, Andrzej Z; Friesen, Ryan M; Martin, Gilles E et al. (2008) Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. Neuron 59:274-87
Luo, Feng; Li, Zhixin; Treistman, Steven N et al. (2007) Confounding effects of volatile anesthesia on CBV assessment in rodent forebrain following ethanol challenge. J Magn Reson Imaging 26:557-63
Roberto, Marisa; Treistman, Steven N; Pietrzykowski, Andrzej Z et al. (2006) Actions of acute and chronic ethanol on presynaptic terminals. Alcohol Clin Exp Res 30:222-32
Ortiz-Miranda, S; Dayanithi, G; Custer, E et al. (2005) Micro-opioid receptor preferentially inhibits oxytocin release from neurohypophysial terminals by blocking R-type Ca2+ channels. J Neuroendocrinol 17:583-90

Showing the most recent 10 out of 33 publications