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-r eleasing hormone (LHRH) on opioid receptor-mediated changes in cyclic AMP (cAMP). Prostaglandin E-1 (PGE(1), 1 mu M) caused a dramatic incre ase in cAMP levels. Treatment with 10 mu M morphine (MOR) significantl y inhibited the stimulatory effect of PGE(1). LHRH (0.8 mu M) caused a n increase in the basal level of intracellular cAMP and potentiated th e stimulatory effect of PGE(1) on cAMP accumulation. In cells pretreat ed with LHRH the inhibitory effect of MOR on cAMP accumulation was sig nificantly attenuated. An LHRH antagonist had no effect on cAMP. The i nvolvement of pertussis toxin (PTX)-sensitive G proteins in the action s of LHRH was studied. PTX increased the stimulatory effect of PGE(1) on cAMP and attenuated the inhibitory effect of MOR. However, PTX pret reatment prevented the effects of LHRH on the intracellular actions of PGE(1) but exerted an additive effect with LHRH in blocking the MOR-i nduced decrease in cAMP levels. We conclude that LHRH attenuates the i nhibitory, opioid receptor-mediated effect of MOR on intracellular cAM P accumulation in SK-N-SH cells, and that the G protein-independent me chanism may be involved in LHRH-induced attenuation of the inhibitory effect of MOR on neuronal cAMP.