Abstract
Abstract: :
Purpose: Our laboratory has previously demonstrated the ability of opioid receptor agonists to decrease intraocular pressure as well as increase the levels of intracellular calcium and inositol phosphates in iris-ciliary bodies (ICBs). Inositol phosphate production can be augmented via stimulation of PLC through an interaction with either the Gα subunit of Gq or Gi-ßγ subunits. The aim of the current study is to investigate the role of Gi-ßγ subunits in delta opioid agonist-mediated signaling in the isolated rabbit ICB. Methods: Isolated ICBs were incubated in buffer containing [3H]myoinositol for 90 min. The labeled tissue was washed three times with nonradioactive buffer containing LiCl (10 mM) for 15 min. The delta agonist, SNC80, and phosducin (Gi-ßγ subunit scavenger) were incubated for 1 hr. Inositol phosphate production was measured by ion exchange chromatography. Results: The relatively selective delta opioid receptor agonist, SNC80, produced a concentration-dependent increase in the levels of inositol phosphates in the ICB. In the presence of 1 nM SNC80, levels of inositol phosphates in the ICB rose 340 12.5 % of control. In the presence of phosducin (1 nM), SNC80 (1 nM)-induced increase in inositol phosphate production was completely abolished. Phosducin alone produced no significant change in the levels of the inositol phosphates. Conclusion: The delta-opioid receptor agonist, SNC80 produced concentration dependent effects on inositol phosphate formation. The increase in inositol phosphate formation induced by SNC80 (1 nM) was inhibited by the Gi-ßγ subunit scavenger, phosducin. These results indicate that free Gi-ßγ subunits play a role in delta opioid receptor-mediated PLC activation and subsequent increase in inositol phosphate levels in the rabbit iris-ciliary body. Thus, this activity could be involved in delta-opioid agonist-induced alterations in aqueous humor dynamics.
Keywords: 581 signal transduction: pharmacology/physiology • 348 ciliary body • 580 signal transduction