PMID- 1762064
OWN - NLM
STAT- MEDLINE
DCOM- 19920207
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 259
IP  - 3
DP  - 1991 Dec
TI  - Effects of GABA in the morphine-tolerant longitudinal muscle, myenteric plexus 
      preparation of the guinea pig.
PG  - 1094-101
AB  - The effect of chronic treatment with morphine via pellet implantation on the 
      sensitivity of the longitudinal smooth muscle-myenteric plexus of the guinea pig 
      ileum to the contractile effects of gamma-aminobutyric acid (GABAA)-receptor 
      agonists was assessed. GABA and muscimol elicited concentration-dependent 
      contractions of the longitudinal smooth muscle which were due to the release of 
      acetylcholine because the contractile effects were markedly attenuated by 
      atropine (10 nM). The contractile action of GABA agonists does not involve an 
      intermediate step mediated by nicotinic receptors because the 
      concentration-response curves for GABA were unaffected by hexamethonium (1 mM). 
      Bicuculline (10 microM) produced nearly equivalent rightward shifts of the 
      concentration-response curves for both GABA and muscimol, indicating mediation of 
      the contractile effects of these agents by GABAA receptors. Chronic exposure to 
      morphine via pellet implantation did not alter the sensitivity of this 
      preparation to either GABA or muscimol. This is in contrast to the development of 
      supersensitivity of the longitudinal smooth muscle-myenteric plexus to other 
      excitatory agonists (nicotine, 5-hydroxytryptamine and potassium), which 
      accompanies the development of tolerance to opioids. GABA induces depolarization 
      of myenteric neurons that is observed most prominently in AH neurons and rarely 
      in S neurons. The stimulatory effects of nicotine and of GABA were inhibited by 
      morphine (a predominantly mu opioid agonist) and by U50,488H (a predominantly 
      kappa opioid agonist). The results are discussed within the context that 
      supersensitivity to neuronal stimulants of the myenteric plexus in 
      morphine-tolerant preparations is limited to substances which depolarize S 
      neurons.
FAU - Taylor, D A
AU  - Taylor DA
AD  - Department of Pharmacology and Toxicology, West Virginia University Health 
      Sciences Center, Morgantown.
FAU - Leedham, J A
AU  - Leedham JA
FAU - Bennett, L E
AU  - Bennett LE
FAU - Fleming, W W
AU  - Fleming WW
LA  - eng
GR  - 5 R01 DA 03773/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Animals
MH  - Drug Tolerance
MH  - Electrophysiology
MH  - Guinea Pigs
MH  - Ileum/drug effects/innervation
MH  - Male
MH  - Morphine/*pharmacology
MH  - Muscle, Smooth/*drug effects/innervation
MH  - Myenteric Plexus/cytology/*drug effects/physiology
MH  - Neurons/drug effects/physiology
MH  - Time Factors
MH  - gamma-Aminobutyric Acid/*pharmacology/physiology
EDAT- 1991/12/01 00:00
MHDA- 1991/12/01 00:01
CRDT- 1991/12/01 00:00
PHST- 1991/12/01 00:00 [pubmed]
PHST- 1991/12/01 00:01 [medline]
PHST- 1991/12/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1991 Dec;259(3):1094-101.