Abstract
Bovine corneas were treated in vitro with various drug regimens and cyclic AMP, protein kinase and glycogen synthase activities were determined in each tissue extract. Isoproterenol (alone) did not increase corneal cyclic AMP under any condition tested. The phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine (IBMX), produced a maximal 2·7-fold increase over control cyclic AMP values. Combinations of isoproterenol (or other β -adrenergic agonists) and IBMX stimulated cyclic AMP up to 25-fold over control. These increases were blocked completely by propranolol. Prostaglandin E 2 (with IBMX) was the only other drug tested which caused a significant increase (6·7-fold over control) in corneal cyclic AMP. Protein kinase activity was stimulated proportionally by cyclic AMP increases up to 8-fold over control. At this point the protein kinase activity ratio was essentially 1·0, indicating complete activation of the enzyme. Glycogen synthase activity decreased sharply in response to increases in corneal cyclic AMP and protein kinase activity. Maximal enzyme inhibition required only fourfold increases in cyclic AMP and approximately half-maximal stimulation of cyclic AMP-dependent protein kinase. These data indicate the conditions necessary to stimulate cyclic AMP in the cornea and the physiological relevance of cyclic AMP increases in terms of its effects on other corneal enzymes.
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