PMID- 8271202
OWN - NLM
STAT- MEDLINE
DCOM- 19940131
LR  - 20190512
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 469
DP  - 1993 Sep
TI  - Morphine tolerance and inhibition of oxytocin secretion by kappa-opioids acting 
      on the rat neurohypophysis.
PG  - 365-86
AB  - 1. The present study investigated the mechanisms by which endogenous opioids 
      regulate oxytocin secretion at the level of the posterior pituitary gland. 
      Effects of the selective kappa-agonist U50,488 on oxytocin secretion were studied 
      in urethane-anaesthetized lactating rats. Oxytocin secretion in response to 
      electrical stimulation (0.5 mA, matched biphasic 1 ms pulses, 50 Hz, 60-180 
      pulses) of the neurohypophysial stalk was bioassayed on-line by measuring 
      increases in intramammary pressure, calibrated with exogenous oxytocin. 
      Intravenous (I.V.) U50,488 inhibited electrically stimulated oxytocin secretion, 
      without affecting mammary gland sensitivity to oxytocin. The inhibition was dose 
      related, with an ID50 of 441 (+194, -136) micrograms/kg and was naloxone 
      reversible. Antagonism of endogenous beta-adrenoceptor activation by propranolol 
      (1 mg/kg) reduced the potency of U50,488. The selective mu-agonist morphine (up 
      to 5 mg/kg), had no effect on electrically stimulated oxytocin secretion, but 
      depressed the mammary response to oxytocin. 2. In lactating rats given 
      intracerebroventricular (I.C.V.) morphine infusion for 5 days to induce tolerance 
      and dependence, I.V. U50,488 still inhibited electrically stimulated oxytocin 
      secretion, but the ID50 was reduced to 170 (+78, -54) micrograms/kg; thus at the 
      posterior pituitary the sensitivity of kappa-receptors is enhanced rather than 
      reduced in morphine-tolerant rats, indicating the absence of cross-tolerance. In 
      these rats, naloxone produced a large, sustained, fluctuating increase in 
      intramammary pressure indicating morphine-withdrawal excitation of oxytocin 
      secretion; I.V. U50,488 diminished this response, confirmed by radioimmunoassay, 
      demonstrating the independence of mu- and kappa-receptors regulating oxytocin 
      secretion. 3. In pregnant rats, I.C.V. infusion of morphine from day 17-18 of 
      pregnancy delayed the start of parturition by 4 h, but did not significantly 
      affect the progress of parturition once established, indicating tolerance to the 
      inhibitory actions of morphine on oxytocin secretion in parturition, and lack of 
      cross-tolerance to endogenous opioids restraining oxytocin in parturition. 4. 
      Neurointermediate lobes from control and I.C.V. morphine-infused virgin rats were 
      impaled on electrodes and perifused in vitro. Vasopressin and oxytocin release 
      from the glands was measured by radioimmunoassay. Each gland was exposed to two 
      periods of electrical stimulation (13 Hz, for 3 min). Naloxone (5 x 10(-6) M) was 
      added before the second stimulation; half the lobes from each I.C.V. treatment 
      were exposed to 5 x 10(-5) M morphine throughout.(ABSTRACT TRUNCATED AT 400 
      WORDS)
FAU - Russell, J A
AU  - Russell JA
AD  - Department of Physiology, University Medical School, Edinburgh.
FAU - Coombes, J E
AU  - Coombes JE
FAU - Leng, G
AU  - Leng G
FAU - Bicknell, R J
AU  - Bicknell RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Analgesics)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 11000-17-2 (Vasopressins)
RN  - 36B82AMQ7N (Naloxone)
RN  - 50-56-6 (Oxytocin)
RN  - 67198-13-4 
      (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer)
RN  - 76I7G6D29C (Morphine)
RN  - 9Y8NXQ24VQ (Propranolol)
SB  - IM
MH  - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer
MH  - Analgesics/pharmacology
MH  - Animals
MH  - Biological Assay
MH  - Drug Tolerance
MH  - Electric Stimulation
MH  - Female
MH  - Injections, Intraventricular
MH  - Labor, Obstetric/drug effects
MH  - Lactation/physiology
MH  - Morphine/administration & dosage/*pharmacology
MH  - Morphine Dependence/physiopathology
MH  - Naloxone/pharmacology
MH  - Oxytocin/*metabolism
MH  - Pituitary Gland, Posterior/*drug effects/metabolism/physiology
MH  - Pregnancy
MH  - Propranolol/pharmacology
MH  - Pyrrolidines/pharmacology
MH  - Radioimmunoassay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Opioid, kappa/*drug effects
MH  - Vasopressins/metabolism
PMC - PMC1143875
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
PMCR- 1993/09/01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
PHST- 1993/09/01 00:00 [pmc-release]
AID - 10.1113/jphysiol.1993.sp019818 [doi]
PST - ppublish
SO  - J Physiol. 1993 Sep;469:365-86. doi: 10.1113/jphysiol.1993.sp019818.