A selective a2-adrenergic agonist, lofexidine, significantly reduced intraocular pressure (lOP) in intact ocular normotensive NZW rabbits, producing a differential dose-dependent decrease in IOP in'the ipsilateral and contralateral eye. Contralateral IOP reduction was most observable at low doses. Unilateral superior cervical ganglionectomy and extraocular muscle excision studies were undertaken to elucidate the factors influencing differential IOP reduction by lofexidine. Similar significant contralateral decreases in IOP were noted when the agent was applied to either the intact or operated eye. Biochemical studies demonstrated that lofexidine inhibited isoproterenol-stimulated adenylcyclase in isolated iris-ciliary body preparations. Yohimbine, an α2-adrenergic antagonist, blocked this inhibitory response. Hence, these observations suggested that lofexidine's site of IOP reduction was probably at the cellular level.

The present investigation is concerned with determining the role of calcium, phospholipids, and phospholipid metabolites on transepithelial sodium and water transport in response to antidiuretic hormone (ADH). These studies utilize the frog skin for determining sodium transport and amphibian urinary bladder for water flow measurements and scanning electron microscopy of cell surface morphology. The results demonstrate that phospholipids and phospholipid metabolites containing arachidonic acid stimulate transepithelial sodium transport through amiloride sensitive channels and the action of these lipids involves the synthesis of prostaglandins. These lipids also inhibited the increase in water flow induced by ADH, and this effect was prevented with prostaglandin synthesis inhibitors. Prostaglandins alter intracellular calcium concentrations and agents effecting calcium metabolism alter cell surface morphology and the changes in surface substructure induced by ADH. These observations support the hypothesis that alterations in membrane permeability to water and ions may involve metabolism of membrane phospholipids and prostaglandin biosynthesis.