An assessment of the antagonistic activity of reactive blue 2 at P1- and P2-purinoceptors: supporting evidence for purinergic innervation of the rabbit portal vein.
A comparison of the effect of the putative adenosine 5'-triphosphate (ATP) antagonist, reactive blue 2, was made on the inhibitory responses to exogenous purines and non-adrenergic, non-cholinergic nerve stimulation in the rabbit portal vein, a preparation possessing both P1- and P2Y-purinoceptors, and on the excitatory responses to alpha, beta-methylene ATP in the rat portal vein where P2X-purinoceptors are present. In the ergotamine-contracted rabbit portal vein, ATP, adenosine and isoprenaline induced concentration-dependent relaxations. Reactive blue 2 (10-50 microM) produced a 2-9-fold shift to the right of the concentration-response curve to ATP, while the responses to adenosine and isoprenaline were not significantly altered. The inhibition of ATP assessed in the concentration-response curves appeared to be non-competitive. Electrical field stimulation of the ergotamine-contracted rabbit portal vein produced frequency-dependent relaxations that were abolished following incubation with tetrodotoxin (1 microM) and were inhibited by reactive blue 2 (30-50 microM), in a concentration-dependent manner. The rat portal vein contracted in response to the application of exogenous noradrenaline and alpha, beta-methylene ATP. Responses to both alpha, beta-methylene ATP (a P2X-purinoceptor agonist) and noradrenaline were not significantly inhibited by concentrations of reactive blue 2 that produced inhibition of the P2Y-mediated responses of the rabbit portal vein. In conclusion, it is suggested that reactive blue 2 is a non-competitive P2Y-purinoceptor antagonist, although the drug has a narrow range of activity and non-specific side effects become apparent at high concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004878:Ergotamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011169:Portal Vein / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity; D014227:Triazines / Q000494:pharmacology*
D011983:Receptors, Purinergic; D014227:Triazines; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; C012842:Cibacron Blue F 3GA; D000244:Adenosine Diphosphate; D004878:Ergotamine