PMID- 3020332
OWN - NLM
STAT- MEDLINE
DCOM- 19861121
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 39
IP  - 17
DP  - 1986 Oct 27
TI  - Central, stereoselective receptors mediate the acute effects of opiate 
      antagonists on luteinizing hormone secretion.
PG  - 1493-99
AB  - Although a central site of acute opiate action in regulating luteinizing hormone 
      (LH) secretion has been suggested by the ability of centrally implanted opiate 
      antagonists to increase LH levels, opiate antagonists are lipophilic and could 
      influence the pituitary in situ. Also, the physiological significance of opiate 
      receptor blockade with antagonists rests on the assumed, but untested, 
      stereoselectivity of these receptors. Therefore, a lipophobic quaternized 
      derivative of naltrexone (MRZ 2663-Naltrexone methobromide) and dextro- (+) and 
      levo- (-) stereoisomers of naloxone were used to study the site- and 
      stereoselectivity of gonadotropin responses to opiate antagonists in vivo. Male 
      rats were injected intracerebroventricularly (icv) or intravenously (iv) with the 
      quaternary or tertiary congeners of naltrexone and subcutaneously (sc) with (-) 
      or (+)-naloxone. Rats injected icv with 20 ug of quaternary naltrexone displayed 
      significant increases in serum luteinizing hormone (LH). The onset of the 
      response was rapid with serum LH levels being significantly elevated 15 minutes 
      after the injection and returning to basal levels 30 minutes later. Rats injected 
      iv with 10 mg/kg of quaternary naltrexone failed to show significant LH 
      responses. Rats injected either centrally or periphally with equivalent doses of 
      tertiary naltrexone showed LH responses that were similar to those found in 
      animals injected icv with quaternary naltrexone. As little as 0.5 mg/kg of 
      (-)-naloxone resulted in significant elevations in serum LH that were higher than 
      those elicited by up to 10 mg/kg of (+)-naloxone, indicating that this effect of 
      naloxone is stereoselective. These data support the argument that opioids can 
      acutely modulate LH secretion through actions at stereoselective opioid receptors 
      in the central nervous system.
FAU - Blank, M S
AU  - Blank MS
FAU - Mann, D R
AU  - Mann DR
FAU - Daugherty, D T
AU  - Daugherty DT
FAU - Sridiran, R
AU  - Sridiran R
FAU - Murphy, J R
AU  - Murphy JR
LA  - eng
GR  - HD15073/HD/NICHD NIH HHS/United States
GR  - HD21880/HD/NICHD NIH HHS/United States
GR  - RR00165/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (Receptors, Opioid)
RN  - 0RK7M7IABE (methylnaltrexone)
RN  - 36B82AMQ7N (Naloxone)
RN  - 5S6W795CQM (Naltrexone)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Injections, Intraventricular
MH  - Luteinizing Hormone/*metabolism
MH  - Male
MH  - Naloxone/*pharmacology
MH  - Naltrexone/analogs & derivatives/*pharmacology
MH  - Quaternary Ammonium Compounds
MH  - Rats
MH  - Receptors, Opioid/*metabolism
MH  - Stereoisomerism
EDAT- 1986/10/27 00:00
MHDA- 1986/10/27 00:01
CRDT- 1986/10/27 00:00
PHST- 1986/10/27 00:00 [pubmed]
PHST- 1986/10/27 00:01 [medline]
PHST- 1986/10/27 00:00 [entrez]
AID - 0024-3205(86)90378-4 [pii]
AID - 10.1016/0024-3205(86)90378-4 [doi]
PST - ppublish
SO  - Life Sci. 1986 Oct 27;39(17):1493-99. doi: 10.1016/0024-3205(86)90378-4.