Synergistic interaction between opioid receptor blockade and alpha-adrenergic stimulation on luteinizing hormone-releasing hormone (LHRH) secretion in vitro.
The effects of opioid receptor blockade, alpha-adrenergic receptor stimulation and concomitant opioid blockade and adrenergic stimulation on LHRH neurosecretion was examined in tissue culture using perifused preoptic area-mediobasal hypothalamic (POA-MBH) explants. Blockade of opioid receptors using naloxone (NAL) resulted in increased (p less than 0.05) LHRH secretion from POA-MBH explants obtained from intact postpubertal female rats. After washout of the NAL-medium, basal release rate was reset to a lower baseline. Subsequent exposure of POA-MBH explants to phenylephrine (PHEN), an alpha-adrenergic agonist, resulted in a slight but statistically insignificant increase in LHRH release from adult explants. The attenuated response to PHEN may have been due to a sustained inhibition of LHRH release following the NAL exposure since PHEN not preceded by NAL resulted in a marked stimulation of LHRH release. In three separate experiments, the LHRH response in postpubertal rat explants to simultaneous PHEN and NAL was greater and more prolonged than the responses to either of the substances alone. This study demonstrates that the stimulatory effects of PHEN are much more profound in the presence of opioid receptor blockage. The observations of the stimulatory effects of PHEN and NAL potentiating each other also suggest that separate mechanisms of LHRH control by each class of neurotransmitter are present. Similar to the postpubertal rat explants, explants obtained from prepubertal rats increased LHRH release in response to NAL and showed a sustained inhibition of LHRH release following washout of NAL. Explants obtained from prepubertal rats also significantly increased LHRH release in response to PHEN.(ABSTRACT TRUNCATED AT 250 WORDS)
Clough
R W
RW
Department of Anatomy, Southern Illinois University School of Medicine, Carbondale.
Hoffman
G E
GE
Sladek
C D
CD
D000818:Animals; D046508:Culture Techniques; D004357:Drug Synergism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*
D011957:Receptors, Opioid; D010656:Phenylephrine; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D011189:Potassium Chloride