Intracellular polyamine levels are involved in NMDA-evoked nitric oxide production in chick retina cells

The NMDA-sensitive glutamate receptor complex can be modulated by numerous drugs and endogenous substances such as polyamines. We studied the pathway of arginine/nitric oxide/cyclic GMP in cultured chick retina cells through NMDA receptor activation, seen as a function of both differentiation stages of culture and intracellular polyamine levels. In our experimental conditi ons, the nitric oxide synthase activity was stimulated by NMDA from three t o four times between embryonic day (E) 8 plus 5 days in vitro (C) and E8C7. The NMDA response was blocked by MK-801 (10 mu M) by >60% at stage E8C5. D uring culture differentiation, the NMDA-induced increase in nitric oxide sy nthase activity at the E8C5 stage was blocked by preliminary incubation (24 h) of the cells with alpha-difluoromethylornithine, the inhibitor of polya mine biosynthesis. This effect was assessed by a reduction of NMDA-evoked c yclic GMP formation in polyamine-depleted retina cells. Thus, intracellular polyamine levels are involved in NMDA-evoked nitric oxide production. Our results indicate that (a) the developmental pattern of polyamine levels can be associated with the modulation of NMDA-evoked events and (b) the NMDA-m ediated effects have been reduced in alpha-difluoromethylornithine-treated cell cultures. These observations provide evidence for a physiological inte raction between polyamines and NMDA-sensitive glutamate receptors during di fferentiation stages of cultured chick retina cells.