“…All three presumptive intracellular phenomena associated with pineal c~l-adrenoceptors, i.e. phosphatidylinositol hydrolysis (Smith et aL, 1979), cGMP synthesis (Zatz, 1982) and PGEe release (Ritta and Cardinali, 1982), could be implicated in pineal PDE activation inasmuch as: (i) some products ofphosphatidylinositol metabolism are very effective in stimulating cyclic nucleotide PDE partially purified from bovine brain (Tai and Tai, 1982); (ii) cGMP at low concentrations stimulates rat brain PDE activity (Murakami et aL, 1983); (iii) PGE2, which increases pineal cAMP levels (Ritta and Cardinali, 1981), may augment low-Km PDE activity by a substrate-mediated effect (Oleshansky and Neff, 1975;Minneman and Iversen, 1976 a). Additionally other changes, like modification of affinity of fl-adrenoceptor sites or of coupling of these receptors with adenylate cyclase could be involved (Leblanc and Cianarello, 1984).…”