Pharmacology of a Ca(2+)-influx pathway activated by emptying the intracellular Ca2+ stores in HL-60 cells: evidence that a cytochrome P-450 is not involved.

In HL-60 cells, inhibition of the endoplasmic-reticular Ca2+ pump by thapsigargin leads to the emptying of this intracellular Ca2+ store and a subsequent activation of plasma-membrane Ca2+ influx through a non-voltage-dependent pathway. The elevated intracellular free Ca2+ concentration ([Ca2+]i) produced and maintained by this Ca2+ inflow was used to examine the potency of various compounds to inhibit this influx mechanism. As expected, specific blockers of known Ca2+ channels, such as nifedipine, omega-conotoxin GVIA and ryanodine were without effect.

EP3, but not EP2, FP, or TP prostanoid-receptor stimulation may reduce intraocular pressure.

Stimulation of DP, but not TP or FP, prostanoid receptors has previously been shown to reduce intraocular pressure (IOP) in rabbits. However the role of EP receptors (EP1, EP2, and EP3 subtypes) has not been studied extensively. Sulprostone, RS-61565, and RS-20216 have been studied for effects on rabbit IOP, and their prostanoid-receptor profiles characterized.

Rat paw-lick/muscle irritation model for evaluating parenteral formulations for pain-on-injection and muscle damage.

A two-phase assay was developed in the rat to evaluate parenteral formulations intended for intramuscular administration for the induction of both acute pain-on-injection and delayed pain/discomfort at the injection site (secondary to muscle damage). Phase 1 of the assay assessed pain-on-injection using a modified version of the previously published rat paw-lick assay. Adult male CD rats (10/group) were given subplantar (footpad) injections of 0.