Evidence that the neuroleptic fluphenazine replaces Ca(2+) and adjusts the noradrenaline induced cyclic adenosine monophosphate synthesis in the rat retina.
Intact rat retinae were incubated in Krebs-Ringer media with noradrenaline (NA) in the presence (0.75 mM) or absence of extracellular Ca(2+) and at relatively high (10 mM) or low (1 mM) theophylline concentrations. Depending on the incubation conditions we found that the neuroleptic fluphenazine (FLU) affected cAMP-synthesis separately from cAMP-degradation of the NA-cAMP system in the retina. The main results were: At a relatively high theophylline concentration of 10 mM, where cAMP synthesis alone is operative, and at 0.75 Ca(2+) we measured with 50 ?M NA a NA-response of 110 pmol cAMP/mg prot. At a low theophylline concentration of 1 mM and again at 0.75 mM Ca(2+) both cAMP-synthesis and -breakdown are operative. In this condition we found the NA-response of 26 pmol cAMP/mg prot. to be raised by 10 ?M FLU to 130 pmol cAMP/mg prot. This enhancing effect might be due to inhibition of degradation of NA-induced cAMP by FLU. In the absence of extracellular calcium and again at 10 mM theophylline, 10 ?M FLU raised the NA response nearly 4-fold from 42 pmol cAMP/mg prot. to 153 pmol cAMP/mg prot. The lowest effective concentration for obtaining this enhancing effect was 10 ?M FLU and the effect is characterized by an apparent K(m) of 0.5 ?M. The use of 10 mM theophylline in this condition suggests that this FLU-Ca(2+) effect is confined to the synthesis part of the NA-cAMP system. The effect points to a replacement of an intramembraneous Ca(2+) function by FLU.


CONCLUSIONS
our results suggest that FLU inhibits degradation of NA-induced synthesis of cAMP and that the neuroleptic renders the NA-response less dependent on extracellular Ca(2+).
Wassenaar
J S
JS
Department of Neurophysiology of the University of Groningen, Bloemsingel 10, 9712 KZ Groningen, The Netherlands.
Korf
J
J
Schrage
C
C