16, 16 dimethyl PGE2: evidence that it has properties different from the parent compound in vascular smooth muscle

16, 16 dimethyl PGE2 (dmPGE2) differs from its parent compound, PGE2, in the way in which it affects vascular reactivity in the isolated perfused mesenteric vascular bed of the rat. Increasing concentrations of PGE2 progressively increase response amplitudes to both noradrenaline and potassium but have no effect on baseline pressure. PGE1 does not change potassium responses but has a biphasic effect on noradrenaline responses, increasing them at low concentrations and inhibiting them at high ones: it has no effect on baseline pressure. PG12 progressively inhibits noradrenaline responses but has no effect on potassium responses: it does not influence baseline pressure in this preparation. PGF2 alpha, like PGE2, enhances responses to both noradrenaline and potassium but, unlike PGE2, strongly elevates baseline pressure. dmPGE2 progressively enhanced responses to potassium, had a biphasic effect on responses to noradrenaline, and strongly raised baseline pressure. Its effects were therefore different from PGE2 and shared properties of the other PGs. This analogue must be used with caution as a guide to the physiological effects of PGE2 itself. The superior mesenteric preparation, which responds very differently to different PGs may be a valuable tool for determining the changes in properties brought about by manipulation of the parent PG molecules.