Molecular mechanisms underlying calcium current modulation by nociceptin.
Nociceptin is a non-opioid peptide that modulates pain response. One of mechanism underlying its analgesic action is the inhibition of voltage-dependent calcium current (ICa), similar to that of opioids. We investigated the molecular mechanism by which nociceptin inhibits ICa using sensory neurons and a heterologous expression system. ICa inhibition by nociceptin was voltage-dependent, exhibited the slowing of activation kinetics and prepulse facilitation, and was blocked by N-ethylmaleimide, indicating the involvement of Gi/Go protein. ICa inhibition by nociceptin was primarily mediated through binding to its own receptor, ORL-1, but not through affecting other mu-opioid receptors. Thus, our results strongly demonstrate that heterologous cross-talk between ORL1 and muOR is not involved in the ICa inhibition by nociceptin.
Yeon
Kyu-Young
KY
Department of Physiology, College of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Sim
Mi-Young
MY
Choi
Se-Young
SY
Lee
Sung Joong
SJ
Park
Kyungpyo
K
Kim
Joong Soo
JS
Lee
Jong-Heun
JH
Lee
Kyung-Mi
KM
Oh
Seog Bae
SB
D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018847:Opioid Peptides / Q000494:pharmacology* / Q000502:physiology; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human