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 cervica l ganglion (SCG). The adenosine-induced hyperpolarization and muscarin e-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 extern al carotid nerve. Depression of the response to muscarine by adenosine was similar for both nerve trunks. 2 The effects of adenosine and cyc lic nucleotides on the d.c. potential and the depolarization to muscar ine were examined by recording via the ICN. Adenosine at concentration s up to 1 mM produced concentration-dependent hyperpolarizations. Hype rpolarization induced by 100 muM adenosine was unaffected by 1 muM tet rodotoxin or the muscarinic M1-receptor antagonist pirenzepine (0.3 mu M). In contrast, hyperpolarizations to 100 muM adenosine were signific antly reduced by 10 muM 8-phenytheophylline (55 +/- 7 muV vs 15 +/- 9 muV, P<0.01, n=4). Two agents known to increase intracellular cAMP, i. e. 8-bromocyclic-adenosine-3'-5'monophosphate (8BrcAMP) and isoprenali ne, depolarized ganglia. Depolarizations to 100 nm mucarine were signi ficantly depressed by adenosine (100 muM) by 26+/-2% (n=61), but unalt ered by 8BrcAMP or cyclic guanosine-3'-5'monophosphate. 3 Dipyridamole and hydroxy-nitro-benzylthioguanosine (inhibitors of adenosine transp ort) and erythro-6-amino-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibi tor of adenosine deaminase), potentiated the depression by adenosine o f the response to muscarine, and the hyperpolarization to adenosine re spectively. However, there was no evidence to support the hypothesis t hat there was spontaneous release of endogenous adenosine under the co nditions of study, as dipyridamole or EHNA did not alter the control d .c. potential or the depolarization to muscarine. 4 It is concluded th at the ability of adenosine to hyperpolarize and depress the response of the rat SCG to muscarine is due to the direct activation of postsyn aptic somatodendritic P1-purinoceptors and unlikely to be mediated by an increase in intracellular cAMP. In addition the rat SCG has mechani sms for both the uptake and inactivation of adenosine.