Prostaglandins of the E series inhibit release of noradrenaline in rat hypothalamus by a mechanism unrelated to classical alpha 2 adrenergic presynaptic inhibition.
The effects of eight different prostanoid derivatives (PGs) on the in vitro release of noradrenaline (NA) from rat hypothalamic slices are reported. Prostaglandin E2 (10(-8)-10(-5) M), which does not interfere with the [3H]NA uptake mechanism, inhibited [3H]NA release induced by K+-evoked depolarization. The rank order of inhibition of release of NA for the PGs was: PGE2 greater than PGE1 greater than PGA2 greater than 16, 16-dimethyl-PGE2 greater than 11-epi-PGE2 greater than or equal to 8-iso-PGE2 greater than PGF2 alpha greater than PGD2. It has recently been shown that PGs of the E series specifically bind with a high affinity to membrane preparations of rat hypothalamus. A similar rank order was found for the activity of these PGs in displacing [3H]PGE2 from its binding sites, suggesting that the effect of PGEs on release of NA is mediated by an interaction with PGE2 receptors. Under the same experimental conditions, 10(-6) M clonidine (an alpha 2 adrenoceptor agonist) diminished, and 10(-6) M yohimbine (an alpha adrenoceptor antagonist) increased [3H]NA release, supporting the existence of alpha 2 auto-inhibition. Exposure to 10(-6) M of the alpha 1, alpha 2 adrenergic receptor antagonist phentolamine, a concentration which by itself had no effect on overflow of [3H]NA, blocked the inhibitory effect of clonidine, but failed to antagonize the inhibitory action of PGE2. Moreover, the action of clonidine and yohimbine remained unaffected when PG synthesis was blocked with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D007031:Hypothalamus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D011188:Potassium; D009638:Norepinephrine