P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminalsin an in vitro intra-arterially perfused rat tongue preparation

1. A novel in vitro intra-arterially perfused adult rat tongue-nerve prepar ation was used to explore the possible actions of P2X purinoceptor agonists (ATP and alpha,beta-methylene ATP (alpha,beta-meATP)) on sensory nerve ter minals innervating the rat tongue. We made whole-nerve recordings of the tr igeminal branch of the lingual nerve (LN), which conducts general sensory i nformation (pain, temperature, touch, etc.), and the chorda tympani (CT), w hich conducts taste information. Changes in LN and CT activity following in tra-arterial application of P2X agonists were compared. 2. In seven preparations, bolus close-arterial injection of ATP (30-3000 mu M, 0.1 ml) or alpha,beta- meATP (10-300 mu M, 0.1 ml) induced a rapid (< 1 s after injection), dose-related increase in LN activity that decayed with in a few seconds. The minimal concentration of ATP (100 mu M) required to e licit a response was about 10-fold higher than that of alpha,beta-meATP (10 mu M). Bolus injection of ATP or alpha,beta-meATP induced a moderate decre ase in firing frequency in three of seven CT preparations. 3. LN responses to P2X agonists showed signs of rapid desensitisation with the peak frequency of discharge being smaller when the agonists were applie d at short intervals. Suramin (200 mu M) or PPADS (200 mu M) applied by int ra-arterial perfusion each antagonised the rapid increase in LN activity fo llowing application of alpha,beta-meATP (100 mu M). 4. Capsaicin (10 mu M, 0.1 ml, n = 5 preparations) was injected intra-arter ially to desensitise nociceptive fibres, This was found to Mock (n = 2) or greatly reduce (n = 3) the excitatory effects of alpha,beta-meATP (100 mu M , 0.1 ml) on LN activity, implying that only capsaicin sensitive nociceptiv e fibres in LN were responsive to P2X agonists. 5. In contrast to the consistent excitatory responses in LN activity follow ing fast application of P2X agonist;s as bolus, a variable and moderate cha nge in discharge rate of LN and no change in CT activity (n = 5) was observ ed after applying ATP (100-300 mu M, n = 21) or alpha,beta-meATP (100-300 m u M, n = 14) by intra-arterial perfusion. The variable responses in LN acti vity to slow perfusion in contrast to close-arterial bolus injection are co nsistent with activation of the rapidly desensitising P2X(3) receptors. 6. In summary, ATP anti alpha,beta-meATP preferentially activate general se nsory afferent fibres (LN) but not taste fibres (CT). We suggest that the i ncrease in whole-nerve activity of LN following application of P2X agonists represents activation of nociceptive fibres which possess P2X(3) receptors . Our data indicate that ATP and P2X(3) receptors may play a role in nocice ption, rather than taste sensation in the tongue.