Pharmacological evidence that methylene blue inhibits noradrenaline neuronal uptake in the rat vas deferens.
We report that the classical guanylate cyclase inhibitor methylene blue (MB, 1 microM or 10 microM), but not the selective guanylate cyclase inhibitor 1H-[1,2,4]oxidazolo[4,3-a]quinoxalin-1-one (1 microM) or nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (100 microM), causes a shift to the left in the concentration-response curve for noradrenaline in the isolated rat vas deferens preparations. The main objective of our study was to investigate the pharmacological mechanism by which MB increases the sensitivity of the rat vas deferens to noradrenaline. According to the presented results, MB did not change rat vas deferens sensitivity to methoxamine or noradrenaline in the presence of desipramine (0.1 microM). The pre-contracted rat vas deferens relaxation induced by isoproterenol was also not significantly changed by MB (1 microM). Thus, we suggest that MB increases rat vas deferens sensitivity through neuronal uptake inhibition without interfering in either the nitrergic mechanism or guanylate cyclase activity.
Chies
Agnaldo B
AB
Laboratory of Pharmacology, School of Medicine of Marilia, 17519-030, SP, Brazil. agnaldochies@hotmail.com
Custódio
Ricardo C
RC
de Souza
Gregório L
GL
Corrêa
Fernando M A
FM
Pereira
Oduvaldo C M
OC
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002395:Catecholamines / Q000493:pharmacokinetics; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000493:pharmacokinetics; D008751:Methylene Blue / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D017609:Barium Compounds; D002395:Catecholamines; D002712:Chlorides; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; C024986:barium chloride; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008729:Methoxamine; D007545:Isoproterenol; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine