ACTION OF PURINE AND PYRIMIDINE NUCLEOTIDES ON THE RAT SUPERIOR CERVICAL-GANGLION

1 Using a grease-gap technique, we have investigated the effects of pu rine and pyrimidine nucleotides on the d.c. potential of the rat isola ted superior cervical ganglion (SCG). 2 Of the purines tested, adenosi ne, adenosine 5'-triphosphate (ATP), beta,gamma-methylene-adenosine 5' -triphosphate (beta,gamma-MeATP) at up to 300 muM produced concentrati on-dependent hyperpolarizations, whereas 2-methyl-thio-ATP (2-Me.S.ATP ) and alpha,beta-methylene-ATP (alpha,beta-MeATP) depolarized ganglia. Of the pyrimidines tested, uridine 5'-triphosphate (UTP) produced con centration-dependent depolarizations and cytosine 5'-triphosphate (CTP ) at 1000 mum produced considerably smaller but significant depolariza tions. In contrast uridine 5'-monophosphate (UMP) at 1000 mum hyperpol arized ganglia. The relative order of potency of purines and pyrimidin es to depolarize ganglia was:- UTP>alpha,beta-MeATP>> CTP > 2-Me.S.ATP and to hyperpolarize ganglia was:- adenosine = beta,gamma-MeATP > ATP > UMP. 3 The ability of purines and pyrimidines to alter the depolari zing response caused by muscarine and of purines to alter depolarizati on induced by gamma-aminobutyric acid (GABA) was determined. The relat ive order of potency of nucleotides in depressing submaximal depolariz ation caused by muscarine (100 nm) was: adenosine = ATP > beta,gamma-M eATP whereas 2-Me. S.ATP, alpha,beta-MeATP and UTP did not significant ly alter depolarization caused by muscarine. At 100 mum beta,gamma-MeA TP and adenosine but not ATP potentiated GABA-induced depolarizations. 4 Hyperpolarizations caused by adenosine, ATP, beta,gamma-MeATP and U MP and depolarizations caused by alpha,beta-MeATP were enhanced in med ium containing reduced concentrations of calcium (0.1 mm) and potassiu m (2 mm). In this medium 8-phenyltheophylline abolished hyperpolarizat ions caused by adenosine and reversed hyperpolarizations caused by ATP into depolarizations. Suramin (300 muM), a P2-purinoceptor antagonist , significantly reduced the depolarizing response caused by alpha,beta -MeATP and significantly increased hyperpolarizations caused by ATP an d beta,gamma-MeATP. Suramin (300 muM) did not significantly alter depo larizations caused by 1,1-dimethyl-4-phenylpiperazinium (10 muM), pota ssium (3 mm) or muscarine (100 nm) and significantly potentiated depol arizations caused by UTP (100 muM). 5 It is concluded that the rat SCG contains P1-purinoceptors that hyperpolarize the ganglion and diminis h sensitivity to muscarine, and P2X-purinoceptors that depolarize the SCG. There is also some evidence to suggest the presence of receptors for UTP, i.e., pyrimidinoceptors, which depolarize SCG neurones.