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

1 Using a grease-gap technique, we have investigated the effects of purine and pyrimidine nucleotides on the d.c. potential of the rat isolated superior cervical ganglion (SCG). 2 Of the purines tested, adenosine, adenosine 5'-triphosphate (ATP), beta,gamma-methylene-adenosine 5'-triphosphate (beta,gamma-MeATP) at up to 300 muM produced concentration-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 concentration-dependent depolarizations and cytosine 5'-triphosphate (CTP) at 1000 mum produced considerably smaller but significant depolarizations. In contrast uridine 5'-monophosphate (UMP) at 1000 mum hyperpolarized ganglia. The relative order of potency of purines and pyrimidines 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 depolarizing response caused by muscarine and of purines to alter depolarization induced by gamma-aminobutyric acid (GABA) was determined. The relative order of potency of nucleotides in depressing submaximal depolarization caused by muscarine (100 nm) was: adenosine = ATP > beta,gamma-MeATP whereas 2-Me. S.ATP, alpha,beta-MeATP and UTP did not significantly alter depolarization caused by muscarine. At 100 mum beta,gamma-MeATP and adenosine but not ATP potentiated GABA-induced depolarizations. 4 Hyperpolarizations caused by adenosine, ATP, beta,gamma-MeATP and UMP and depolarizations caused by alpha,beta-MeATP were enhanced in medium containing reduced concentrations of calcium (0.1 mm) and potassium (2 mm). In this medium 8-phenyltheophylline abolished hyperpolarizations 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 and beta,gamma-MeATP. Suramin (300 muM) did not significantly alter depolarizations caused by 1,1-dimethyl-4-phenylpiperazinium (10 muM), potassium (3 mm) or muscarine (100 nm) and significantly potentiated depolarizations caused by UTP (100 muM). 5 It is concluded that the rat SCG contains P1-purinoceptors that hyperpolarize the ganglion and diminish 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.