The electrically stimulated release of [3H]noradrenaline from nucleus tractus solitarii slices in vitro is modulated via mu-opioid receptors.
The electrically stimulated release of [3H]noradrenaline ([3H]NA) from slices of the nucleus tractus solitarii (NTS) from the rat in vitro was inhibited by the alpha 2-adrenoceptor agonist, clonidine, in a concentration-dependent manner and enhanced by the alpha 2-adrenoceptor antagonist, yohimbine. Phenylephrine, isoprenaline, carbachol, quinpirole and SKF 38393, all at 10(-6) M, did not affect the stimulus-evoked release of [3H]NA. The opioid peptides, alpha- and gamma-endorphin, did not have a significant effect on the stimulus-evoked release of [3H]NA; however, beta-endorphin reduced it in a concentration-dependent manner. [Leu5]Enkephalin also reduced [3H]NA release, but higher concentrations were necessary. The selective delta opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), as well as the selective kappa opioid receptor agonist, U-69593, were not effective. The selective mu opioid receptor agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), concentration dependently reduced the stimulus-evoked release of [3H]NA to the same extent as beta-endorphin did. Naloxone, while having no effect on stimulus-evoked [3H]NA release, antagonized the effect of DAGO. These results corroborate that the release of NA from noradrenergic terminals in the NTS region of the medulla oblongata of the rat is modulated via alpha 2-adrenoceptors and suggest that the release of NA in the NTS in rats is also modulated via mu opioid receptors.
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
K
K
Arakawa
W
W
De Jong
A H
AH
Mulder
D H
DH
Versteeg
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D001615:beta-Endorphin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004745:Enkephalins; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D010656:Phenylephrine; D001615:beta-Endorphin; D009638:Norepinephrine