The dipeptide carnosine constricts rabbit saphenous vein as a zinc complex apparently via a serotonergic receptor.
1. The endogenous dipeptide carnosine (beta-alanyl-L-histidine), at 0.1-10 mM, provokes sustained contractures in rabbit saphenous vein rings with greater efficacy than noradrenaline (NA). 2. The effects of carnosine are specific; anserine and homocarnosine are ineffective, as are carnosine's constituent amino acids histidine and beta-alanine. 3. Maximum carnosine-induced tension is enhanced by Zn ions (e.g. to 127.5 +/- 13.1% of control at 10 microM total Zn concentration, Zntot) and the sensitivity to carnosine potentiated (mean [carnosine] required for half-maximal tension, K1/2, reduced from 1.23 mM to 17.0 microM carnosine with 15 microM Zntot). 4. The dipeptide apparently acts as a zinc-carnosine complex. The effects of carnosine at concentrations of 1 microM to 10 mM in the presence of 1-100 microM Zntot, can be described as a unique function of the concentration of Zn-carnosine, with an apparent K1/2 for the complex of 7.4 x 10(-8) M. 5. Contractures are reduced at low [Ca2+], unaffected by adrenoceptor antagonists, but can be blocked by serotonergic receptor antagonists including ketanserin and methiothepin. 6. Competition between albumin and carnosine for Zn ions, as might occur in plasma, can be demonstrated experimentally. 7. The mode of action of carnosine is virtually unique: a vascular muscle receptor apparently transduces the action of a dipeptide in the form of a metal chelate.
MRC Clinical Research Initiative in Heart Failure, University of Glasgow, UK.
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O'Dowd
J J
JJ
O'Dowd
D J
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Miller
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002336:Carnosine / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry
D000317:Adrenergic alpha-Antagonists; D002614:Chelating Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012709:Serum Albumin; D014662:Vasoconstrictor Agents; D002336:Carnosine; D015032:Zinc; D009638:Norepinephrine