The effects of pyrimidines and purines on the d.c. potential of the rat isolated superior cervical ganglion (SCG) have been examined by a grease-gap technique to determine the structure-activity requirements of the receptor activated by pyrimidines, i.e. a pyrimidinoceptor. 2. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl (ZTP), the pyrimidines, cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP) and thymidine 5'-triphosphate (TTP) and the purines, adenosine 5'-triphosphate (ATP; in the presence of an A1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (1 microM)), adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), guanosine 5'-triphosphate (GTP), inosine 5'-triphosphate (1TP) depolarized ganglia in a concentration-dependent manner. The relative order of ZTP and purine 5'-triphosphates in depolarizing ganglia was ZTP > or = ATP gamma S > > ATP > or = ITP = GTP, and for the pyrimidine 5'-triphosphates UTP > TTP > or = CTP. Depolarizations evoked by ATP gamma S were followed by concentration-dependent hyperpolarizations at 100 and 1000 microM. 3. At concentrations of between 0.1 microM and 1 mM, uridine 5'-diphosphate (UDP), uridine 5'-diphosphoglucose (UDPG) and uridine 5'-diphosphoglucuronic acid (UDPGA) evoked significant and concentration-dependent depolarizations, whereas uridine 5'-monophosphate (UMP), uridine and uracil were inactive or produced small (< 45 microV) depolarizations. The relative order of potency of uridine analogues in depolarizing ganglia was UDP > or = UTP > UDPG > UDPGA > > uracil > or = UMP = pseudouridine > or = uridine. At 3 and 10 mM, uridine produced concentration-dependent hyperpolarizations. Nikkomycin Z, a nucleoside resembling UTP (viz. the triphosphate chain at the 5'-position on the ribose moiety being replaced by a peptide), was inactive between 1 microM and 1 mM. Generally, a concentration of 10 mM was required before thymidine, 6-azathymine, 6-azauracil or 6-azauridine depolarized ganglia. 4. Suramin (300 microM), a P2-purinoceptor antagonist, significantly depressed depolarizations evoked by alpha, beta-methylene-ATP (alpha, beta-MeATP; 100 microM), ATP gamma S (100 microM), CTP (1 mM), GTP (1 mM), ZTP (30 microM) and ATP (300 microM) in the presence of DPCPX (1 microM). Suramin reversed a small depolarization evoked by UMP (1 mM) into a small hyperpolarization. In contrast depolarizations evoked by UDP, UTP, UDPG (all at 100 microM) and TTP (300 microM) were unaltered or enhanced by suramin. 5. It is concluded that the rat SCG contains distinct nucleotide receptors including a P2-purinoceptor (activated by alpha, beta-MeATP, ATP, GTP, ITP and ZTP) and a pyrimidinoceptor (activated by UTP, UDP, UDPG, UDPGA and TTP). The pyrimidinoceptor on rat SCG neurones had specific structure activity requirements with the di- and triphosphates of uridine being the most effective depolarizing agonists examined.
