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 microM 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 microM produced considerably smaller but significant depolarizations. In contrast uridine 5'-monophosphate (UMP) at 1000 microM 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 microM 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 microM), 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 microM) did not significantly alter depolarizations caused by l,l-dimethyl-4-phenylpiperazinium (10 microM), potassium(3 mM) or muscarine (100 nM) and significantly potentiated depolarizations caused by UTP (100 microM).5.It is concluded that the rat SCG contains PI-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.