Antisense oligodeoxynucleotides to G-protein α-subunit subclasses identify a transductional requirement for the modulation of normal feeding dependent on GαOA subunit

Carlos R. Plata-Salamán, Charlie D. Wilson, Gayatri Sonti, Jeffrey Paul Borkoski, Jarlath M.H. ffrench-Mullen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A variety of G-protein-coupled receptors are proposed to participate in the modulation of ingestive behavior and in the mode of action of antiobesity drugs. In the present study, we investigated the involvement of G-protein α-subunit subclasses (molecular transducers of multiple chemical signals) in the control of ingestive behavior. We report here that the chronic intracerebroventricular (i.c.v.) microinfusion for 72 h (via osmotic minipumps) with antisense phosphothio-oligodeoxynucleotides corresponding to G-protein α-subunitO common (to OA and OB) and OA subclasses decrease the nighttime food intake without affecting water intake in rats. Computerized analyses of the microstructure of feeding indicate that the GαOA antisense depresses feeding by reducing meal frequency, while meal size and meal duration increased slightly, but not significantly. The effects of GαO common and GαOA antisense on feeding are specific since the chronic i.c.v. microinfusion of sense to GαO common or GαOA, antisense to the related subclass GαOB, and antisense to other G-protein α-subunits (GαS, GαQ, Gα11 and Gαi common) had no effect on food or water intake. The observed effects by GαO common and GαOA antisense imply a direct action in the central nervous system since the chronic subcutaneous microinfusion of GαO common and GαOA antisense in doses equivalent or two-fold higher relative to those administered centrally had no effect on food intake. The chronic microinfusion of GαO common antisense drastically decreased the levels of GαO protein detected in immunoblots of hypothalamic ventromedial nuclei. The results suggest that the G-protein α-subunit subclass GαOA is critical for the integrative modulation of normal feeding behavior, and that changes in its activity may be associated with modifications of feeding. These studies also show a novel approach to study the molecular basis of specific behaviors by manipulating elements of the transductional systems.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalMolecular Brain Research
Volume33
Issue number1
DOIs
StatePublished - Jan 1 1995

Fingerprint

Oligodeoxyribonucleotides
Protein Subunits
GTP-Binding Proteins
Meals
Eating
Drinking
Ventromedial Hypothalamic Nucleus
Anti-Obesity Agents
Behavior Control
Feeding Behavior
G-Protein-Coupled Receptors
Transducers
Central Nervous System
Proteins

Keywords

  • Anorexia
  • Antisense oligonucleotide
  • Feeding
  • Food intake
  • G-protein
  • Intracerebroventricular administration
  • Meal pattern
  • Nervous system
  • Rat

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Antisense oligodeoxynucleotides to G-protein α-subunit subclasses identify a transductional requirement for the modulation of normal feeding dependent on GαOA subunit. / Plata-Salamán, Carlos R.; Wilson, Charlie D.; Sonti, Gayatri; Borkoski, Jeffrey Paul; ffrench-Mullen, Jarlath M.H.

In: Molecular Brain Research, Vol. 33, No. 1, 01.01.1995, p. 72-78.

Research output: Contribution to journalArticle

Plata-Salamán, Carlos R. ; Wilson, Charlie D. ; Sonti, Gayatri ; Borkoski, Jeffrey Paul ; ffrench-Mullen, Jarlath M.H. / Antisense oligodeoxynucleotides to G-protein α-subunit subclasses identify a transductional requirement for the modulation of normal feeding dependent on GαOA subunit. In: Molecular Brain Research. 1995 ; Vol. 33, No. 1. pp. 72-78.
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