Extracellular potassium controls responsiveness of the noradrenergic cAMP system in the rat retina to fluphenazine.
The effects of fluphenazine (FLU) on the noradrenaline (NA) induced cAMP-synthesis in intact rat retinae were studied as a function of extracellular K(+)- and Ca(2+)-ions. Thus NA-induced cAMP levels were measured after incubating intact rat retinae with 50 ?M NA in the presence or absence of FLU and in the presence of 1 or 10 mM theophylline. Results were: (1) Experimental condition a: standard NA-responses were measured after incubating retinae at 0.75 mM Ca(2+), at 10 mM theophylline, at 10 ?M FLU and at 2 and 0 mM K(+). FLU does not affect the NA-response at 2 mM K(+) significantly; however, it inhibits the NA-response at 0 mM K(+) in this condition. (2) Experimental condition b: NA-responses were measured after incubating retinae at 0.125 mM Ca(2+), 10 mM theophylline, 10 ?M FLU and at 2 and 0 mM K(+). At 2 mM K(+) FLU replaces a Ca(2+) function probably connected with the synthesis part of the NA-cAMP system and NA-responses in this low Ca(2+) condition are consequently enhanced by FLU; however, FLU inhibits the NA-response at 0 mM K(+) in this condition. (3) Experimental condition c: NA-responses were measured after incubating retinae at 0.75 mM Ca(2+), 1 mM theophylline, 10 ?M FLU and at 2 and 0 mM K(+). At 2 mM K(+) FLU enhances the NA-response by further inhibition of the degradation part of the NA-cAMP system; FLU inhibits the NA-response at 0 mM K(+) in this condition. (4) The inhibitions of the NA-responses by FLU at 0 mM K(+) in all three conditions a, b and c showed an apparent K(m) of 1 ?M. (5) Low concentrations of K(+) (0.4-0.8 mM) maintain the property of FLU to enhance the NA-responses at condition b (0.125 mM Ca(2+)) and at condition c (1 mM theophylline). Results suggest that the activation of NA-receptor coupled adenylate cyclases (NA-AC-ases) by NA, resulting in activation of phosphodiesterase activity by the NA-elevated cAMP-levels, is sustained by (a) membraneous factor(s) connected to the NA-receptor. This (these) factor(s) is (are) switched off in the absence of K(+). Evidence has been presented, that Ca(2+) and FLU do not have access to this intramembraneous factor-enzyme activating moiety of the NA-cAMP system at 0 mM K(+). Between 0.4 and 0.8 mM K(+) the factor-enzyme-NA-receptor complex is still intact.
Wassenaar
J S
JS
Department of Neurophysiology of the University of Groningen, Bloemsingel 10, 9712 KZ Groningen, The Netherlands.
Schrage
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C
Veringa
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