Antagonism by Calcium of the Inhibitory Action of Prostaglandin E₂ on Sympathetic Neuro‐transmission in the Cat Spleen

Abstract

HEDQVIST, P. i.!ntagonism by calcium of the inhibitory action of prostaglandin EZ on sympathetic neurotransmission in the cut spleen. Acta physiol. scand. 1970. 80. 269-275. Experiments werz carried out with the isolated, perfused cat spleen and bovine splenic nerve trunk to study the target for prostaglandin E2 induced inhibition of noradrenaline release from sympathetic nervzs. Increasing the calcium concentration in the medium perfusing the spleeen was found to increase the outflow of noradrenaline to nerve stimuiation and to antagonize the inhibitory action of prostaglandin Ez on this parameter. Prostaglandin E2 did not affect the noradrenaline releasing effect of tyramine. Atropine did not alter the inhibitory effect of prostaglandin Ez on noradrenaline release. Prostaglandin Ez did not change the amplitude of action potentials in bovine splenic nerves. There is thus no support for a blocking action on nerve conduction. It is concluded that prostaglandin E2 may prevent calcium from gaining access to those sites in sympathetic nerve terminals where it promotes secretion of noradrenaline. L

Prostaglandin Release From Cat and Dog Spleen

“…The responses of the cat spleen to sympathetic nerve stimulation were modified in the presence of exogenous prostaglandins E and prostaglandin synthetase inhibitors (Hedqvist & Brundin, 1969;Hedqvist, 1969Hedqvist, , 1970aHedqvist, , 1970bHedqvist, Stjirne & Wennmalm, 1971;Ferreira et al, 1973). The responses of the dog spleen, on the other hand, were unaffected by prostaglandins E 1, E2 or F2Ca .…”

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

“…As shown schematically in Figure 7, the following presynaptic receptors have been postulated: (a) muscarinic inhibitory cholinoceptors (Loffelholz and Muscholl, 1969;Steinsland, Furchgott & Kirpekar, 1973;Langer, Enero, Adler-Graschinsky, Dubocovich & Giorgi, 1976); (b) dopamine inhibitory receptors (Langer, 1973;Enero & Langer, 1975;Long, Heintz, Cannon & Kim, 1975); (c) opiate inhibitory receptors, which are activated by morphine and also by the naturally occurring pentapeptides met and leu-enkephalin (Hughes, Kosterlitz & Leslie, 1975 (Hedqvist, 1970;Stjmrne, 1973;Dubocovich & Langer, 1975;Hedqvist, 1976); (e) adenosine inhibitory receptors (Hedqvist & Fredholm, 1976); (f) angiotensin II facilitatory receptors (Starke, 1970(Starke, , 1971Hughes & Roth, 1971) and (g) nicotinic facilitatory receptors (Lindmar, Loffelholz & Muscholl, 1968;Loffelholz, 1970).…”

Enhanced Release of Dopamine-β-Hydroxylase from Sympathetic Nerves by Calcium and Phenoxybenzamine and Its Reversal by Prostaglandins

“…Absence of calcium also prevents the release of DOHase from the perfused bovine spleen during electrical stimulation of the splenic nerve (6). The antagonistic action of PGE2 and PGE, on the increased release of DOHase in the presence of increased calcium is similar to their inhibition of the effect of 5 mM calcium on norepinephrine outflow in the perfused cat-spleen (17). This indicates that prostaglandins interfere with the action of calcium and, thus, may play a regulatory role in the c.lcium-deper.dent secretion of norepinephrine and DOHase.…”

“…Since prostaglandin E2 (PGE2) blocks the enhanced outflow of norepinephrine from perfused organs caused by either high concentrations of calcium (17) or phenoxybenzamine (18), its effect on release of DOHase was also examined.…”