Relationship between desensitization and sequestration of muscarinic cholinergic receptors in two neuronal cell lines.

Agonist-induced sequestration and desensitization of muscarinic receptors was studied in two cell lines that each express differentially-coupled receptors. The NG108-15 glioma x neuroblastoma hybrid cells have muscarinic receptors coupled only to the inhibition of adenylate cyclase, whereas SK-N-SH human neuroblastoma cells have muscarinic receptors coupled only to the turnover of phosphoinositide. In both NG108-15 and in SK-N-SH cells, muscarinic agonists caused a rapid, temperature-dependent, loss of binding sites for [3H] N-methylscopolamine. In contrast, the density of binding sites for [3H] quinuclidinyl benzilate remained almost unchanged after treatment with carbachol. Since carbachol also caused a redistribution of muscarinic receptors from the plasma membrane to a lighter membrane fraction, the loss of binding sites for [3H] N-methyl-scopolamine was interpreted as being due to sequestration of receptors. In addition to agonist-induced sequestration, muscarinic agonists also caused desensitization of the receptor-mediated response in NG108-15 cells. In SK-N-SH cells, however, no such desensitization of the receptor-mediated response was found, despite the agonist-induced sequestration of receptors. These findings demonstrate that agonist-induced sequestration of receptors does not always lead to desensitization of receptors.

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group.

PURPOSE: The analgesic efficacy and safety of topical ketorolac tromethamine 0.5% ophthalmic solution (Acular) in photorefractive keratectomy was compared to its vehicle. METHODS: Double-masked, multicenter, study of 200 patients dosed with 1 drop of study medication (ketorolac or vehicle) in the operated eye immediately after surgery (eye patched), with four-times daily dosing for the next 3 days starting 3 hours after surgery. Mepergan Fortis was available as an escape pain medication. RESULTS: Patients (102) in the ketorolac group reported significantly greater pain relief and less pain intensity than the vehicle group (98) at several time points (P < or = .039). Time to first use of escape medication was significantly longer in the ketorolac than the vehicle group (mean, 16.0 vs 5.5 hr; P =.001). Time to complete pain relief was significantly shorter in the ketorolac than the vehicle group (mean, 41.3 vs 50.3 hr; P =.022). Significantly fewer patients in the ketorolac group reported sleep difficulties, ocular discomfort, or other difficulties. Few adverse events were reported with ketorolac treatment (less than with vehicle), and there were no clinically significant changes in any of the safety variables monitored. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution (Acular) is safe and significantly more effective than vehicle in alleviating pain following photorefractive keratectomy.