Two aromatic residues regulate the response of the human oxytocin receptor to the partial agonist arginine vasopressin.
We investigated the mechanisms that regulate the efficacy of agonists in the arginine-vasopressin (AVP)/oxytocin (OT) receptor system. In this paper, we present evidence that AVP, a full agonist of the vasopressin receptors, acts as a partial agonist on the oxytocin receptor. We also found that AVP becomes a full agonist when two aromatic residues of the oxytocin receptor are replaced by the residues present at equivalent positions in the vasopressin receptor subtypes. Our results indicate that these two residues modulate the response of the oxytocin receptor to the partial agonist AVP.
Chini
B
B
CNR Cellular and Molecular Pharmacology Center, Milan, Italy.
Mouillac
B
B
Balestre
M N
MN
Trumpp-Kallmeyer
S
S
Hoflack
J
J
Hibert
M
M
Andriolo
M
M
Pupier
S
S
Jard
S
S
Barberis
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010121:Oxytocin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000819:agonists* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014668:Vasotocin / Q000378:metabolism
D018045:Receptors, Oxytocin; D001127:Arginine Vasopressin; D010121:Oxytocin; C045427:oxytocin, Thr(4)-Gly(7)-; C052292:oxypressin; D014668:Vasotocin