L-AP4 inhibition of depolarization-evoked cGMP formation in rat cerebellum

The effects of the group III mGluR agonist, L-2-amino-4-phosphonobutyrate (L-AP4), on depolarization-stimulated cGMP levels in adult rat cerebellar slices were determined. L-AP4 elicited a concentration-dependent, complete inhibition of cGMP formation stimulated by 4-aminopyridine (4-AP; 1 mM), yielding an IC50 value of 4.2 +/- 1.6 microM (n = 3). The 4-AP response was also reduced by the P-type Ca2+ channel toxins omega-conotoxin MVIIC (3 microM; 39 +/- 7% inhibition) and omega-Agatoxin IVA (30 nM; 53 +/- 4%), and was abolished in the absence of Ca2+ or in the presence of Co2+. The inhibitions of the 4-AP cGMP response by 10 microM L-AP4 and 30 nM omega-Agatoxin IVA were not additive, indicating that part of the actions of L-AP4 in the cerebellum involves the modulation of P-type Ca2+ channels.