B. Bucher, ORL1 receptor-mediated inhibition by nociceptin of noradrenaline release from perivascular sympathetic nerve endings of the rat tail artery, N-S ARCH PH, 358(6), 1998, pp. 682-685
In the present study the effect of the opioid heptadecapeptide nociceptin,
also termed orphanin FQ, an endogenous ligand for the orphan receptor named
ORL1 (opioid receptor-like I) receptor, was investigated on [H-3]noradrena
line release induced by electrical field stimulation (24 pulses at 0.4 Hz,
200 mA, 0.3 ms duration) in the rat tail artery in the absence and presence
of an alpha(2)-adrenoceptor antagonist, rauwolscine 3 mu M.
Nociceptin inhibited the electrically-evoked tritiated noradrenaline releas
e in a concentration-dependent manner from rat tail arteries. This inhibito
ry effect of nociceptin was enhanced in the presence of the a2-adrenoceptor
antagonist rauwolscine (maximum inhibition by 25% and 50% in the absence a
nd presence of rauwolscine, respectively). At a supramaximal concentration
(10 mu M), the inhibitory action of DAGO, a selective mu-opioid receptor ag
onist, was less pronounced than that of nociceptin. The inhibitory effect o
f nociceptin was counteracted by naloxone benzoylhydrazone (3 mu M) which b
y itself did not change the stimulation-evoked noradrenaline overflow. Nalo
xone(10 mu M), a non-selective opioid receptor antagonist, did not affect t
he inhibitory effect of nociceptin whereas it abolished that of DAGO.
In conclusion, these results suggest that nociceptin modulates noradrenergi
c neurotransmission by acting on prejunctional ORL1 receptors located on ne
rve terminals innervating the rat tail artery. They also demonstrate that p
rejunctional ORL1 receptors interact with prejunctional alpha(2)-adrenocept
ors. The physiological significance of this phenomenon remains to be determ
ined.