Specific activation of the mu opioid receptor (MOR)
by endomorphin 1 and endomorphin 2
by
Monory K, Bourin MC, Spetea M, Tomboly C, Toth G,
Matthes HW, Kieffer BL, Hanoune J, Borsodi A
Institute of Biochemistry, Biological Research Center,
Hungarian Academy of Sciences, 6701 Szeged, Hungary;
Isotope Laboratory, Biological Research Center,
Hungarian Academy of Sciences, 6701 Szeged, Hungary;
INSERM U-99, Hopital Henri Mondor, 94010 Creteil, France;
UPR 9050 CNRS, 67400 Strasbourg, France.
Eur J Neurosci 2000 Feb; 12(2):577-584

ABSTRACT

The recently discovered endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) were investigated with respect to their direct receptor-binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the mu opioid receptor, an effect reversed by the mu receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2), but they had no influence on cells stably expressing the delta opioid receptor. To further establish the selectivity of these peptides for the mu opioid receptor, brain preparations of mice lacking the mu opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild-type mice with a Kd value of 1.77 nM and a Bmax of 63.33 fmol/mg protein. In membranes of mice lacking the mureceptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the mu opioid receptors.

Analogs
Morphine
Endomorphins
Knockout mice
Endomorphins 1 and 2
Endomorphins and the mouse
The rewards of endomorphin 1
Endomorphins and rodent brains
Adenylyl cyclase superactivation
Endomorphinergic neurons in the CNS
Endomorphins 1 and 2 as antidepressants
Endomorphins and the mu-opioid receptor
Endomorphin 1, dopamine and nitric oxide
Rewarding and psychomotor stimulant effects of endomorphin 1
Endomorphin-1, accumbal dopamine and the mu-opioid receptor

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