Orphanin FQ has an inhibitory effect on the guinea pig ileum and the mouse vas deferens.
The activity of the recently isolated endogenous opioid-like peptide orphanin FQ (OFQ) was measured in two classical bioassays of opioid action. OFQ potently and concentration-dependently suppressed the electrically stimulated contractions of the guinea pig ileum (GPI) and the mouse vas deferens (MVD) with EC50 values of 1.82 +/- 0.16 and 2.97 +/- 0.01 nM, and Emax values of 56 +/- 3% and 96 +/- 4%, respectively. This effect of OFQ, in both the GPI and MVD, was insensitive to the opioid receptor antagonist naloxone. OFQ competed with [3H]diprenorphine binding to mu-, delta- or kappa-opioid receptors stably expressed in Chinese hamster ovary cell lines with IC50 values of 2.1 +/- 0.4, 2.2 +/- 0.3, 0.75 +/- 0.3 microM, respectively. Low affinity for the classical opioid receptors together with the inability of naloxone to antagonize its effect suggest that the inhibitory action of OFQ is mediated via a distinct OFQ receptor in the GPI and MVD. Consequently, the MVD could serve as a valuable bioassay of potential OFQ receptor antagonists.
Zhang
G
G
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Murray
T F
TF
Grandy
D K
DK
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004399:Dynorphins / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects*; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists*; D014649:Vas Deferens / Q000187:drug effects; D000097629:Nociceptin
D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000097629:Nociceptin; C026843:dynorphin (1-13)