ETHANOL TOLERANCE AND DEPENDENCE IN VITRO

  • Richelson, Elliott, (PI)

Project: Research project

Description

The locus of ethanol's pharmacological and addictive effects may be at the
level of the interaction between a neurotransmitter and its receptor in the
synapse. Therefore this proposal focuses on the effects of acute and
chronic ethanol on the functioning of certain receptors which have cyclic
AMP and cyclic GMP as putative second messengers. Cultured human skin
fibroblasts with prostaglandin and Beta-adrenergic receptors mediating
cyclic AMP synthesis and murine neuroblastoma cells (clone N1E-115) with
several receptors (muscarinic, histamine H1, angiotensin 11, bradykinin,
neurotensin and thrombin) mediating cyclic GMP synthesis are being used as
model systems for this work. Studies with human skin fibroblasts will
determine whether results found in animal studies (including our work with
murine neuroblastoma cells) are applicable to human receptors. Studies
with murine neuroblastoma cells may help elucidate the mechanism whereby
ethanol depletes brain levels of cyclic GMP. The prostaglandin and
Beta-adrenergic receptors of human skin fibroblasts will be thoroughly
characterized by biological assay (cyclic AMP production) and by
radioligand binding assay prior to the studies with ethanol. The cyclic
GMP studies with neuroblastoma cells will follow-up on our data showing a
mixed type of inhibition (competitive and noncompetitive) by ethanol of
receptor-mediated cyclic GMP synthesis and an adaptation to this effect of
ethanol upon chronic exposure of cells to this alcohol. Since
receptor-mediated cyclic GMP synthesis involves the turnover of
phospholipids, effects of ethanol on the release of inositol phosphates and
arachidonate acid will be studied.
StatusFinished
Effective start/end date4/1/806/30/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Cyclic GMP
Ethanol
Neuroblastoma
Prostaglandins
Receptors, Adrenergic, beta
Fibroblasts
Neurotransmitter Receptor
Histamine H1 Receptors
Neurotensin
Skin
Inositol Phosphates
Clone Cells
Angiotensins
Second Messenger Systems
Bradykinin
Adenosine Monophosphate
In Vitro Techniques
Thrombin
Biological Assay
Cyclic AMP

ASJC

  • Medicine(all)