Cholinergic, adrenergic, and PGE₁ effects on cyclic nucleotides and growth in cultured corneal epithelium

Effecrs of adrenergic and cholinergic drugs and prostaglandin E₁ on cyclic nucleotide accumulation and parameters of growth and basement membrane synthesis were examined in corneal epithelial cell cultures. 8-bromo-cGMP significantly (p<0.05) enhanced incorporation of labeled thymidine and leucine, as did acetylcholine and carbamylcholine, which elevated cGMP and decreased cAMP/cGMP ratio. Responses to acetylcholine were abolished by atropine and α-bungarotoxin. Precursor incorporation was inhibited by dibutyryl cAMP and adenosine 5'-monophosphate and by norepinephrine, epinephrine, prostaglandin E₁, and theophylline, which significantly elevated cAMP levels and cAMP/cGMP ratio. Propranolol, but not phenoxybenzamine, blocked responses to effective concentrations of norepinephrine. Norepinephrine, PGE₁, and dibutyryl cAMP also significantly elevated uptake of labeled glucosamine and incorporation of labeled proline into collagenase-sensitive protein or the hydroxyproline fraction of protein hydrolysates, while acetylcholine had no effect on parameters of basement membrane synthesis. Propranolol blocked responses to norepinephrine. Results were consistent with a cGMP-mediated stimulatory role of the cholinergic transmitter in corneal epithelial growth regulation, cAMP-mediated β-adrenergic suppression of regrowth and increased basement membrane production after initial injury to the corneal epithelium, and potentiation of the adrenergic effect by prostaglandins.