Luteinizing hormone-releasing hormone (LHRH) attenuates morphine-induced inhibition of cyclic AMP (cAMP) in opioid-responsive SK-N-SH cells.
SK-N-SH cells were used to assess the effects of luteinizing hormone-releasing hormone (LHRH) on opioid receptor-mediated changes in cyclic AMP (cAMP). Prostaglandin E1 (PGE1, 1 microM) caused a dramatic increase in cAMP levels. Treatment with 10 microM morphine (MOR) significantly inhibited the stimulatory effect of PGE1, LHRH (0.8 microM) caused an increase in the basal level of intracellular cAMP and potentiated the stimulatory effect of PGE1 on cAMP accumulation. In cells pretreated with LHRH the inhibitory effect of MOR on cAMP accumulation was significantly attenuated. An LHRH antagonist had no effect on cAMP. The involvement of pertussis toxin (PTX)-sensitive G proteins in the actions of LHRH was studied. PTX increased the stimulatory effect of PGE1 on cAMP and attenuated the inhibitory effect of MOR. However, PTX pretreatment prevented the effects of LHRH on the intracellular actions of PGE1 but exerted an additive effect with LHRH in blocking the MOR-induced decrease in cAMP levels. We conclude that LHRH attenuates the inhibitory, opioid receptor-mediated effect of MOR on intracellular cAMP accumulation in SK-N-SH cells, and that the G protein-independent mechanism may be involved in LHRH-induced attenuation of the inhibitory effect of MOR on neuronal cAMP.
Ratka
A
A
Department of Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello 83209, USA.
Simpkins
J W
JW
D000527:Alprostadil / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009447:Neuroblastoma; D037342:Pertussis Toxin; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D007987:Gonadotropin-Releasing Hormone; D009020:Morphine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000527:Alprostadil