On the site of action and inactivation of adenosine by the rat superior cervical ganglion.

1. Using an extracellular recording technique, we have investigated the site of action of adenosine and muscarine on the rat superior cervical ganglion (SCG). The adenosine-induced hyperpolarization and muscarine-induced depolarization of ganglia were localized to the cell bodies of the ganglia. Responses to muscarine and adenosine were larger when recorded via the internal carotid nerve (ICN) compared with the external carotid nerve. Depression of the response to muscarine by adenosine was similar for both nerve trunks. 2. The effects of adenosine and cyclic nucleotides on the d.c. potential and the depolarization to muscarine were examined by recording via the ICN. Adenosine at concentrations up to 1 mM produced concentration-dependent hyperpolarizations. Hyperpolarization induced by 100 microM adenosine was unaffected by 1 microM tetrodotoxin or the muscarinic M1-receptor antagonist pirenzepine (0.3 microM). In contrast, hyperpolarizations to 100 microM adenosine were significantly reduced by 10 microM 8-phenytheophylline (55 +/- 7 microV vs 15 +/- 9 microV, P < 0.01, n = 4). Two agents known to increase intracellular cAMP, i.e. 8-bromo-cyclic-adenosine-3'-5' monophosphate (8BrcAMP) and isoprenaline, depolarized ganglia. Depolarizations to 100 nM mucarine were significantly depressed by adenosine (100 microM) by 26 +/- 2% (n = 61), but unaltered by 8BrcAMP or cyclic guanosine-3'-5' monophosphate. 3. Dipyridamole and hydroxy-nitro-benzylthioguanosine (inhibitors of adenosine transport) and erythro-6-amino-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase), potentiated the depression by adenosine of the response to muscarine, and the hyperpolarization to adenosine respectively. However, there was no evidence to support the hypothesis that there was spontaneous release of endogenous adenosine under the conditions of study, as dipyridamole or EHNA did not alter the control d.c. potential or the depolarization to muscarine. 4. It is concluded that the ability of adenosine to hyperpolarize and depress the response of the rat SCG to muscarine is due to the direct activation of postsynaptic somatodendritic P1-purinoceptors and unlikely to be mediated by an increase in intracellular cAMP. In addition the rat SCG has mechanisms for both the uptake and inactivation of adenosine.