Methyl orange antagonizes uridine 5' triphosphate and not alpha,beta-methylene-adenosine 5' triphosphate-evoked depolarization of rat superior cervical ganglia.
1. Compared with the effects of adenosine 5' triphosphate (ATP) on the nervous system, the actions of pyrimidine nucleosides and their 5'-nucleotides, such as uridine 5' triphosphate (UTP), have received less attention. In part, this is because there is a need for a selective antagonist for responses mediated by UTP-activated receptors. The objective of this study was to discover such an antagonist. 2. Superior cervical ganglia isolated from male rats were superfused with a physiological salt solution. Responses to alpha,beta-methylene-ATP (alpha,beta-Me-ATP), potassium, adenosine and UTP were determined before and in the presence of 1-300 microM methyl orange. 3. Methyl orange at 1-100 microM did not alter resting potential or depolarizing responses to alpha,beta-Me-ATP, potassium, or adenosine-evoked hyperpolarizations, but at 10 and 100 microM methyl orange significantly antagonized UTP-evoked depolarizations (P < 0.05). 4. Although the antagonistic effects of methyl orange were not dramatic, this is the first report of a putative pyrimidinoceptor antagonist. These observations also support the idea of distinct receptors for UTP and ATP on rat superior cervical ganglia.
Connolly
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GP
Purine NeuroScience Laboratory, Chemical Pathology, Guy's, King's and St Thomas' Medical School, King's College London, London SE1 9RT, UK.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D010477:Perfusion; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology
D001391:Azo Compounds; D007202:Indicators and Reagents; C100258:methyl orange; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D011188:Potassium; D014544:Uridine Triphosphate