Schematic diagram illustrating second messenger pathways possibly involved in regulating pigment granule movement in RPE and entry points for muscarinic regulation. Most evidence suggests a central role for cAMP-dependent phosphorylation events in the induction of pigment granule aggregation in retinal pigment epithelium. Shown in black boxes in this schematic diagram are players in this pathway that have been manipulated experimentally in RPE isolated from bluegill, green sunfish or both. Pathways shown in red indicate possible regulatory inputs from muscarinic receptor activation (see text for a more extensive explanation as well as references). Abbreviations used are as follows (listed alphabetically): 5'-AMP, 5'-adenosine monophosphate; Ca2+, calcium; Ca-CaM, calcium-calmodulin complex; cAMP
, intracellular cyclic adenosine monophosphate; cAMP
, extracellular cyclic adenosine monosphosphate; FSK, forskolin; G
, inhibitory GTP-binding protein; GSF, green sunfish (indicating that this experimental manipulation was only performed on RPE isolated from green sunfish); IBMX, isobutylmethylxanthine (a phosphodiesterase inhibitor); IP
, inositol trisphosphate; M
, muscarinic acetylcholine receptor subtype 2 or 4; M
, muscarinic acetylcholine receptor subtype 1, 3, or 5; OAT, organic anion transporter; PDE, phosphodiesterase; PKI
amide, cAMP-dependent protein kinase inhibitory peptide (amino acids 5–24) with an amide adduct; PLC, phospholipase C; Protein-P, a phosphoprotein; arrows terminating in diamonds signify inhibitory effects; arrows terminating in triangles or barbs signify stimulatory effects.