PMID- 9274973
OWN - NLM
STAT- MEDLINE
DCOM- 19971027
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 331
IP  - 2-3
DP  - 1997 Jul 23
TI  - Central administration of morphine inhibits brain and liver ornithine 
      decarboxylase activity in neonatal rats: involvement of transcription- and 
      non-transcription-dependent mechanisms.
PG  - 145-53
AB  - This study examined whether the developmental deficits usually observed in 
      infants born to opiate addicted mothers could involve effects on ornithine 
      decarboxylase, a growth-controlling enzyme. Intracerebroventricular (i.c.v.) 
      injection of a single dose of morphine (2 microg) to 6-day-old rats markedly 
      decreased basal brain and liver ornithine decarboxylase activity as well as the 
      increases in hepatic ornithine decarboxylase activity produced by subcutaneously 
      (s.c.) administered insulin, an important trophic hormone. Centrally applied 
      morphine acts supraspinally to downregulate peripheral ornithine decarboxylase 
      activity, since s.c. administration of the same dose as used i.c.v. decreased 
      neither basal liver ornithine decarboxylase levels nor tissue responsiveness to 
      insulin. This does not imply that the opiate is unable to affect ornithine 
      decarboxylase when applied systemically. In fact, a robust inhibition of both 
      basal and induced liver ornithine decarboxylase activity was obtained in rat pups 
      given 20 microg of morphine s.c. This larger dose is able to trigger the hepatic 
      ornithine decarboxylase effects presumably by stimulating opiate receptors 
      located at central sites after crossing the blood-brain barrier and penetrating 
      into the brain. Concomitant administration of naloxone plus morphine i.c.v. 
      prevented morphine from downregulating ornithine decarboxylase activity, 
      confirming the participation of supraspinal opioid receptors in morphine 
      ornithine decarboxylase actions. Finally, as was the case for insulin induced 
      stimulation of ornithine decarboxylase activity, i.c.v. injection of morphine 
      markedly diminished insulin induced stimulation of hepatic ornithine 
      decarboxylase mRNA accumulation. In turn, contrary to the inhibition of basal 
      ornithine decarboxylase activity, morphine did not lower basal hepatic ornithine 
      decarboxylase mRNA levels when given alone. Thus, CNS morphine can apparently 
      suppress tissue ornithine decarboxylase expression through both transcriptional 
      and posttranscriptional mechanisms. The evidence obtained suggest that postnatal 
      exposure to opiate drugs might detrimentally affect development by altering 
      normal tissue ornithine decarboxylase ontogeny.
FAU - Bartolome, J V
AU  - Bartolome JV
AD  - Department of Pharmacology, Duke University, Durham, NC 27710, USA.
FAU - Alicke, B
AU  - Alicke B
FAU - Bartolome, M B
AU  - Bartolome MB
LA  - eng
GR  - R01 NS 25738/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Ornithine Decarboxylase Inhibitors)
RN  - 24937-83-5 (Poly A)
RN  - 63231-63-0 (RNA)
RN  - 76I7G6D29C (Morphine)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - Analgesics, Opioid/administration & dosage/*pharmacology
MH  - Animals
MH  - Animals, Newborn/*metabolism
MH  - Blotting, Northern
MH  - Brain/drug effects/*enzymology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hypoglycemic Agents/pharmacology
MH  - Injections, Intraventricular
MH  - Insulin/pharmacology
MH  - Liver/drug effects/*enzymology
MH  - Morphine/administration & dosage/*pharmacology
MH  - Ornithine Decarboxylase/metabolism
MH  - *Ornithine Decarboxylase Inhibitors
MH  - Poly A/metabolism
MH  - RNA/biosynthesis/isolation & purification
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription, Genetic/physiology
EDAT- 1997/07/23 00:00
MHDA- 1997/07/23 00:01
CRDT- 1997/07/23 00:00
PHST- 1997/07/23 00:00 [pubmed]
PHST- 1997/07/23 00:01 [medline]
PHST- 1997/07/23 00:00 [entrez]
AID - S0014-2999(97)01045-5 [pii]
AID - 10.1016/s0014-2999(97)01045-5 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1997 Jul 23;331(2-3):145-53. doi: 10.1016/s0014-2999(97)01045-5.