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.