Pharmacological characterization of rabbit corpus cavernosum relaxation mediated by the tissue kallikrein-kinin system.
1. The roles of the tissue kallikrein-kinin system and nitric oxide (NO) release in Phoneutria nigriventer venom-induced relaxations of rabbit corpus cavernosum (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2. Phoneutria nigriventer venom (10-30 micrograms), porcine pancreatic kallikrein (100 mu), rabbit urinary kallikrein (10 mu), bradykinin (BK, 0.3-3 nmol), acetylcholine (ACh, 0.3-30 nmol) and glyceryl trinitrate (GTN, 0.5-10 nmol) caused relaxations of the RbCC strips. Captopril (1 microM) substantially potentiated Phoneutria nigriventer venom- and BK-induced RbCC relaxations without affecting those elicited by GTN. 3. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3,Thi5,D- Tic7,Oic8]-BK, 50 nM), aprotinin (10 micrograms ml-1) and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val- Gln-NH2 (KIZD-06, 1.3 microM) significantly inhibited Phoneutria nigriventer venom-induced RbCC relaxations, without affecting those provoked by GTN and ACh. The B1 receptor antagonist, [Leu9]des Arg10BK (0.5 microM) and soybean trypsin inhibitor (SBTI, 10 micrograms ml-1) had no effect on Phoneutria nigriventer venom-induced RbCC relaxations. 4. The relaxations induced by Phoneutria nigriventer venom, porcine pancreas kallikrein, BK and ACh were significantly inhibited by N omega-nitro-L-arginine methyl ester (L-NAME, 10 microM) but not by D-NAME (10 microM). L-NAME did not affect GTN-induced relaxations. L-Arginine (300 microM), but not D-arginine (300 microM), significantly reversed the inhibitory effect of L-NAME. 5. Our results indicate that Phoneutria nigriventer venom activates the tissue kallikrein-kininogen-kinin system in RbCC strips leading to NO release and suggest a functional role for this system in penile erection.
Lopes-Martins
R A
RA
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), Brazil.
Antunes
E
E
Oliva
M L
ML
Sampaio
C A
CA
Burton
J
J
de Nucci
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D066298:In Vitro Techniques; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000652:urine; D008297:Male; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013111:Spider Venoms / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D009842:Oligopeptides; D013111:Spider Venoms; C091376:prolyl-phenylalanyl-Aph-seryl-valyl-glycinamide; D009569:Nitric Oxide; C065679:icatibant; D007611:Aprotinin; D001120:Arginine; D002216:Captopril; D007610:Kallikreins; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester