Regulation of arachidonate release, prostaglandin synthesis, and sphincter constriction in the mammalian iris-ciliary body.

In the anterior segment of the eye, phosphoinositides of the iris-ciliary body are the major source of AA for PG biosynthesis. In the past several years, we have demonstrated that these phospholipids are highly enriched in AA and have an extremely high metabolic turnover. We have also discovered that their metabolism by phospholipase C, which leads to the formation of IP3 and DG and the liberation of AA, is controlled by the following Ca2+-mobilizing receptors: alpha 1-adrenergic, M3- or M4-muscarinic cholinergic, substance P, and PGs. The release of IP3, DG, and AA in the iris was also demonstrated under in vivo conditions. Furthermore, it was demonstrated that this release is associated with denervation supersensitivity and subsensitivity of the iris. Two pathways have been demonstrated in the iris through which AA can be released directly from phosphoinositides: (a) Phosphoinositides can be hydrolyzed by phospholipase C, followed by hydrolysis of DG via lipases to liberate AA, and (b) AA can be released directly from phosphoinositides via phospholipase A2. Although the evidence for a link between Ca2+-mobilizing receptors and phospholipase C, via G proteins, has been well established, the precise link between these receptors and phospholipase A2 is still unclear. Our studies indicated that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation. In addition, evidence of a link between the two pathways through the Ca2+ signaling system has been suggested. In the iris, PAF was found to liberate AA from phosphoinositides through the phospholipase A2, but not the phospholipase C pathway, thus emphasizing the role of this pathway in PG synthesis in the eye. These findings demonstrate that AA release and, consequently, PG synthesis in the iris of the eye are exquisitely regulated. In some species, such as bovine, cat and dog, PGs were found to act as full Ca2+ mobilizing agonists. It is possible that PGs function to maintain muscle tone in the resting iris smooth muscle cells, in addition to their involvement in various Ca2+-dependent processes. Our studies indicate that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)