Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat.
We have investigated the influence of endogenous opioids on oxytocin secretion during pregnancy. In blood-sampled conscious rats on days 18 and 21 of pregnancy plasma oxytocin concentration, measured by radioimmunoassay, was significantly increased compared to non-pregnant or post-partum rats. On days 15, 18 and 21 of pregnancy but not in non-pregnant, early pregnant or post-partum rats, the opioid antagonist naloxone caused a significant increase in plasma oxytocin compared to vehicle injection, indicating activation of an endogenous opioid restraint over oxytocin secretion. Electrically stimulated neural lobes isolated from 16- and 21-day pregnant rats released more oxytocin than those from non-pregnant rats. However, naloxone (10(-5) M) was less effective at potentiating, and the kappa-opioid agonist U50,488 (10(-5)M) was less effective at inhibiting, stimulated release at the end of pregnancy than in non-pregnant rats suggesting desensitization of oxytocin nerve terminals to actions of endogenous opioids. Neural lobes from male rats drinking 2% saline for 4 days also showed desensitization of oxytocin nerve endings to naloxone. Neither neural lobe content of dynorphin A(1-8), an endogenous kappa-opioid, nor prodynorphin mRNA expression, measured by in situ hybridization histochemistry in the supraoptic nucleus altered during pregnancy. However, neural lobe content of Met5-enkephalin significantly decreased by day 21 of gestation suggesting enhanced release.(ABSTRACT TRUNCATED AT 250 WORDS)
Douglas
A J
AJ
Department of Physiology, University Medical School, Edinburgh, UK.
Dye
S
S
Leng
G
G
Russell
J A
JA
Bicknell
R J
RJ
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D004399:Dynorphins / Q000378:metabolism; D004558:Electric Stimulation; D004723:Endorphins / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000378:metabolism
D004723:Endorphins; D004745:Enkephalins; D010446:Peptide Fragments; D011498:Protein Precursors; D011759:Pyrrolidines; D012333:RNA, Messenger; D014667:Vasopressins; D009270:Naloxone; D010121:Oxytocin; D004744:Enkephalin, Methionine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C026770:dynorphin (1-8); C033660:preproenkephalin