TY - JOUR
T1 - Analysis of vasodepressor responses to nociceptin and nociceptin analogs in the systemic vascular bed of the anesthetized rabbit in vivo
AU - Champion, H. C.
AU - Bivalacqua, T. J.
AU - Rauchwarger, A.
AU - McWilliams, S. M.
AU - McNamara, D. B.
AU - Kadowitz, P. J.
PY - 1998
Y1 - 1998
N2 - Background: The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein- coupled receptor ORL1. Methods and Results: In the present study, responses to nociceptin, [Tyr1]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascular bed of the rabbit. Nociceptin and [Tyr1]-nociceptin induced dose related decreases in systemic arterial pressure (SAP) when injected in doses of 1-30 nmol/kg intravenous (IV); in terms of relative vasodepressor activity, [Tyr1]-nociceptin and nociceptin were similar in potency. However, nociceptin-(2-17), nociceptin- (1-11), and nociceptin-(1-7) had no effect on SAP when injected in doses up to 30 nmol/kg IV. The decreases in SAP in response to nociceptin and [Tyr1]- nociceptin were not altered by the opioid receptor antagonist naloxone at a time when depressor responses to methionine-enkephalin were reduced significantly. Conclusions: The results of the present study show that vasodepressor responses to nociceptin and [Tyr1]-nociceptin are mediated by the activation of a naloxone-insensitive opioid receptor and are not dependent on the presence of Phe at the N-terminus of the nociceptin sequence. Moreover, the present results show that nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) do not alter SAP in the rabbit, indicating that peptide chain length is important for the expression of vasodepressor activity.
AB - Background: The heptadecapeptide nociceptin, also known as Orphanin FQ, is a recently discovered endogenous ligand for the opioid-like G-protein- coupled receptor ORL1. Methods and Results: In the present study, responses to nociceptin, [Tyr1]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the systemic vascular bed of the rabbit. Nociceptin and [Tyr1]-nociceptin induced dose related decreases in systemic arterial pressure (SAP) when injected in doses of 1-30 nmol/kg intravenous (IV); in terms of relative vasodepressor activity, [Tyr1]-nociceptin and nociceptin were similar in potency. However, nociceptin-(2-17), nociceptin- (1-11), and nociceptin-(1-7) had no effect on SAP when injected in doses up to 30 nmol/kg IV. The decreases in SAP in response to nociceptin and [Tyr1]- nociceptin were not altered by the opioid receptor antagonist naloxone at a time when depressor responses to methionine-enkephalin were reduced significantly. Conclusions: The results of the present study show that vasodepressor responses to nociceptin and [Tyr1]-nociceptin are mediated by the activation of a naloxone-insensitive opioid receptor and are not dependent on the presence of Phe at the N-terminus of the nociceptin sequence. Moreover, the present results show that nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) do not alter SAP in the rabbit, indicating that peptide chain length is important for the expression of vasodepressor activity.
KW - Opioid receptors
KW - Orphanin FQ
KW - Vasodepressor activity
UR - http://www.scopus.com/inward/record.url?scp=0032429380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032429380&partnerID=8YFLogxK
U2 - 10.1177/107424849800300308
DO - 10.1177/107424849800300308
M3 - Article
AN - SCOPUS:0032429380
SN - 1074-2484
VL - 3
SP - 247
EP - 252
JO - Journal of Cardiovascular Pharmacology and Therapeutics
JF - Journal of Cardiovascular Pharmacology and Therapeutics
IS - 3
ER -