Vasorelaxation by casomokinin L, a derivative of beta-casomorphin and casoxin D, is mediated by NK1 receptor.
Casomokinin L (Tyr-Pro-Phe-Pro-Pro-Leu), a derivative of beta-casomorphin and casoxin D, showed endothelium-dependent vasorelaxing activity on the canine mesenteric artery (EC50 = 7 x 10(-8) M). This relaxing activity was partly blocked by 10(-5) M NAME (nitric oxide synthase inhibitor), and the inhibition by NAME was restored by addition of 10(-4) M arginine, suggesting the involvement of nitric oxide as an endothelium-dependent relaxing factor. The relaxing activity was blocked by 10(-8) M CP-99994 and 10(-7) M FK888 (NK1 antagonists), but not by 10(-6) M SR-48968 (NK2 antagonist). Casomokinin L binds to neurokinin NK1 receptors (Ki = 5.8 x 10(-5) M), and lowered blood pressure in SHR (0.1 mg/kg, i.v. and 3 mg/kg, PO). Thus, despite its only three residues in common with substance P, casomokinin L binds to NK1 receptors, relaxes the artery, and exerts an antihypertensive effect.
Fujita
H
H
Nippon Synthetic Chemical Industry Co., Ltd., Osaka, Japan.
Suganuma
H
H
Usui
H
H
Kurahashi
K
K
Nakagiri
R
R
Sasaki
R
R
Yoshikawa
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002364:Caseins; D004151:Dipeptides / Q000494:pharmacology; D004285:Dogs; D004723:Endorphins; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000959:Antihypertensive Agents; D002364:Caseins; D004151:Dipeptides; D004723:Endorphins; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C078949:FK 888; C103113:casomokinin L; C021968:beta-casomorphins; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester