The NOP receptor involvement in both withdrawal- and CCk-8-induced contracture responses of guinea pig isolated ileum after acute activation of κ-opioid receptor.
In isolated guinea-pig ileum (GPI), the κ-opioid acute withdrawal response is under the control of several neuronal signaling systems, including the μ-opioid, the A(1)-adenosine and the CB(1) receptors, which are involved in the inhibitory control of the κ-withdrawal response. After κ-opioid system stimulation, indirect activation of μ-opioid, A(1)-adenosine and CB(1) systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated whether the NOP system is also involved in the regulation of the acute κ-withdrawal response. Interestingly, we found that in GPI preparation, the NOP system is not indirectly activated by the κ-opioid receptor stimulation, but instead this system is able by itself to directly regulate the acute κ-withdrawal response. Specifically, our results clearly highlight first the existence of an endogenous tone of the NOP system in GPI, and second that it behaves as a functional anti-opioid system. We also found that, the NOP receptor system is involved in the regulation of the CCk-8-induced contracture intensity, only when in the presence of the κ-opioid receptor stimulation. This effect seems to be regulated by an activation threshold mechanism. In conclusion, the NOP system could act as neuromodulatory system, whose action is strictly related to the modulation of both excitatory and inhibitory neurotransmitters released in GPI enteric nervous system.
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. p.marini@abdn.ac.uk
Pietro
P
Marini
Luca
L
Romanelli
Daniela
D
Valeri
Maria Grazia
MG
Cascio
Paolo
P
Tucci
Pacifico
P
Valeri
Maura
M
Palmery
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002766:Cholecystokinin; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C410885:cholecystokinin 8