Prejunctional modulation by prostaglandin E2 of noradrenaline release from sympathetic neurones in rabbit aorta.
The modulating effect of prostaglandin E2 (PGE2) on the electrically-evoked 3H-overflow from rabbit isolated aorta preloaded with 3H-noradrenaline was examined. PGE2 (3 x 10(-9)-3 x 10(-7) M) inhibited the stimulation-evoked 3H-overflow (maximum inhibition: 81%; pIC50: 8.1). The inhibition was reversible and inversely related to stimulation frequency (1-30 Hz). Cocaine (3 x 10(-5) M) and corticosterone (4 x 10(-5) M) did not alter the inhibitory effect of PGE2 (3 x 10(-9)-10(-7) M). Rauwolscine (10(-6) M) enhanced the reduction caused by PGE2 (3 x 10(-9)-10(-7) M). Rauwolscine (10(-6) M) alone enhanced the 3H-overflow by 360%. Indomethacin (3 x 10(-6) M) and suprofen (4 x 10(-5) M) did not alter the PGE2 (3 x 10(-9)-10(-7) M)-induced reduction of the 3-H-overflow. Indomethacin (3 x 10(-6) M) and suprofen (4 x 10(-5) M) alone had no effect. We conclude that in the rabbit aorta (1) PGE2 modulates noradrenaline release from sympathetic neurones through a prejunctional inhibitory receptor mechanism; (2) that there is an interaction between alpha 2-adrenoceptors and EP-receptors; (3) that uptake inhibition does not affect the effect of PGE2; and (4) that the influence of endogenous prostaglandins on the noradrenaline release can be excluded.
Jensen
T J
TJ
Department of Pharmacology, School of Medicine, Odense University, Denmark.
Nedergaard
O A
OA
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D018341:Receptors, Adrenergic, alpha-2; D011982:Receptors, Prostaglandin; D015016:Yohimbine; D009638:Norepinephrine