Comparison of the effects of biogenic amines on cyclic GMP and cyclic AMP levels in mouse cerebellum in vitro

Abstract

Norepinephrine (NE) elevates levels of both 3′,5′-guanosine monophosphate (cyclic GMP) and 3′,5′-adenosine monophosphate (cyclic AMP) in incubated slices of mouse cerebellum. As little as 1 μM NE is capable of increasing the level of either cyclic nucleotide. Maximal elevations of cyclic AMP and cyclic GMP levels produced by NE are 15- to 4-fold and 2- to 4-fold, respectively. Dopamine, serotonin and histamine, other biogenic amines considered to be neurotransmitters in CNS, have no effect on mouse cerebellum cyclic nucleotide levels except at relatively high (1 mM) concentrations. NE-induced accumulation of cyclic GMP, but not cyclic AMP, is blocked by omission of Ca 2+ from the incubation media. Theophylline does not alter the effect of this catecholamine on either cyclic nucleotide. In tissue slices incubated in buffered sucrose or in choline-Krebs buffer, NE is still capable of increasing both cyclic GMP and cyclic AMP levels; however, these elevations are less than those observed in brain slices incubated in Krebs-Ringer buffer. NE, in combination with glutamate, produces supra-additive elevations of both cyclic GMP and cyclic AMP levels. However, NE in combination with adenosine or high levels of K + only has a synergistic effect on cyclic AMP and not on cyclic GMP accumulation. The elevation of cyclic AMP levels produced by NE appears to be mediated via both α- and β-adrenergic receptor sites. In contrast, the receptor site(s) mediating cyclic GMP accumulation do not appear to be either typical α- or β-adrenergic receptors.