Methoxamine enhances the release of endogenous noradrenaline from rabbit ear artery: possible involvement of ATP.
The effect of methoxamine, an alpha 1-adrenoceptor agonist, on the electrically-evoked release of endogenous noradrenaline was examined in the isolated rabbit ear artery. Noradrenaline was quantified by high performance liquid chromatography-electrochemical detection. The release of adenine nucleotides and nucleosides by methoxamine was examined using high performance liquid chromatography-fluorescence detection. The release of noradrenaline evoked by electrical field stimulation (EFS) at 4 Hz was reduced by tetrodotoxin 0.3 mumol/l and clonidine 1 mumol/l by approximately 80% and 50%, respectively. On the other hand, methoxamine at 10 but not 1 mumol/l enhanced the release of noradrenaline to approximately twice the control, and the enhancement was prevented by prazosin 1 mumol/l. The facilitatory action of methoxamine was also abolished after desensitization of P2-purinoceptors by alpha,beta-methylene ATP 30 mumol/l as well as by the presumed P2-purinoceptor antagonist suramin given at 10 mumol/l. Exogenous ATP 10 mumol/l significantly enhanced the EFS-evoked release of noradrenaline, and the enhancement was abolished by alpha,beta-methylene ATP and suramin. None of the drugs changed the spontaneous outflow of noradrenaline. These results indicate that endogenous ATP, acting at prejunctional purinoceptors, may participate in the facilitatory effect of methoxamine. Indeed, methoxamine 10 mumol/l significantly enhanced the spontaneous outflow of ATP and, less so, ADP. The methoxamine evoked release of ATP and ADP was antagonized by prazosin 1 mumol/l. It is concluded that methoxamine releases endogenous ATP from postjunctional sites which then, via prejunctional purinoceptors, facilitates action potential-evoked release of noradrenaline in rabbit ear artery.
Department of Pharmacology, Meiji College of Pharmacy, Tokyo, Japan.
R
R
Ishii
K
K
Shinozuka
Y
Y
Kobayashi
K
K
Hattori
T
T
Hashimoto
K
K
Takeuchi
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000378:metabolism; D004423:Ear / Q000098:blood supply; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits
D000227:Adenine Nucleotides; D000255:Adenosine Triphosphate; D008729:Methoxamine; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine