Prostaglandins are known to lower activation threshold to thermal, mechanical, and chemical stimulation in small-diameter sensory neurons. Although the mechanism of prostaglandin action is unknown, agents known to elevate intracellular calcium produce a sensitization that is similar to that produced by prostaglandins. Consistent with the idea of prostaglandin-induced elevations in calcium, prostaglandins might also stimulate the release of neurotransmitter from sensory neurons. We therefore examined whether prostaglandin E2 (PGE2) could enhance the release of the putative sensory transmitter substance P (SP) from isolated neurons of the avian dorsal root ganglion grown in culture. Utilizing the whole-cell patch-clamp recording technique, we also examined whether PGE2 could alter calcium currents in these cells. Exposure of sensory neurons to PGE2 produced a dose-dependent increase in the release of SP. One micromolar PGE2 increased release approximately twofold above basal release, whereas 5 and 10 μM PGE2 increased release by about fourfold. The release evoked by these higher concentrations of PGE2 was similar in magnitude to the release induced by 50 mM KCl. Neither arachidonic acid (10 μM), prostaglandin F(2α) (10 μM), nor the lipoxygenase product leukotriene B4 (1 μM) significantly altered SP release. The addition of 1 μM PGE2 increased the peak calcium currents by 1.8-fold and 1.4-fold for neurons held at potentials of -60 and -90 mV, respectively. The action of PGE2 was rapid with facilitation occurring within 2 min. As with release studies, arachidonic acid, prostaglandin F(2α), and leukotriene B4 had no significant effect on the amplitude of the calcium current. These results suggest that PGE2 can stimulate the release of SP through the activation or facilitation of an inward calcium current. The capacity of PGE2 to facilitate the calcium current in these sensory neurons may be one mechanism to account for the ability of prostaglandins to sensitize sensory neurons to physical or chemical stimuli.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Neuroscience|
|State||Published - 1992|
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