title: P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminals in an in vitro intra-arterially perfused rat tongue preparation.
abstract: A novel in vitro intra-arterially perfused adult rat tongue-nerve preparation was used to explore the possible actions of P2X purinoceptor agonists (ATP and alpha,beta-methylene ATP (alpha, beta-meATP)) on sensory nerve terminals innervating the rat tongue. We made whole-nerve recordings of the trigeminal branch of the lingual nerve (LN), which conducts general sensory information (pain, temperature, touch, etc.), and the chorda tympani (CT), which conducts taste information. Changes in LN and CT activity following intra-arterial application of P2X agonists were compared. In seven preparations, bolus close-arterial injection of ATP (30-3000 microM, 0.1 ml) or alpha,beta-meATP (10-300 microM, 0.1 ml) induced a rapid (< 1 s after injection), dose-related increase in LN activity that decayed within a few seconds. The minimal concentration of ATP (100 microM) required to elicit a response was about 10-fold higher than that of alpha,beta-meATP (10 microM). Bolus injection of ATP or alpha,beta-meATP induced a moderate decrease in firing frequency in three of seven CT preparations. LN responses to P2X agonists showed signs of rapid desensitisation with the peak frequency of discharge being smaller when the agonists were applied at short intervals. Suramin (200 microM) or PPADS (200 microM) applied by intra-arterial perfusion each antagonised the rapid increase in LN activity following application of alpha,beta-meATP (100 microM). Capsaicin (10 microM, 0.1 ml, n = 5 preparations) was injected intra-arterially to desensitise nociceptive fibres. This was found to block (n = 2) or greatly reduce (n = 3) the excitatory effects of alpha,beta-meATP (100 microM, 0.1 ml) on LN activity, implying that only capsaicin-sensitive nociceptive fibres in LN were responsive to P2X agonists. In contrast to the consistent excitatory responses in LN activity following fast application of P2X agonists as bolus, a variable and moderate change in discharge rate of LN and no change in CT activity (n = 5) was observed after applying ATP (100-300 microM, n = 21) or alpha,beta-meATP (100-300 microM, n = 14) by intra-arterial perfusion. The variable responses in LN activity to slow perfusion in contrast to close-arterial bolus injection are consistent with activation of the rapidly desensitising P2X3 receptors. In summary, ATP and alpha,beta-meATP preferentially activate general sensory afferent fibres (LN) but not taste fibres (CT). We suggest that the increase in whole-nerve activity of LN following application of P2X agonists represents activation of nociceptive fibres which possess P2X3 receptors. Our data indicate that ATP and P2X3 receptors may play a role in nociception, rather than taste sensation in the tongue.
authors.affiliation: Autonomic Neuroscience Institute, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: W
authors.initials: W
authors.lastname: Rong
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
authors.forename: K M
authors.initials: KM
authors.lastname: Spyer
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007269:Injections, Intra-Arterial; D008036:Lingual Nerve / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058477:Receptors, Purinergic P2X3; D013268:Stimulation, Chemical; D013498:Suramin / Q000494:pharmacology; D013649:Taste / Q000502:physiology*; D014059:Tongue / Q000098:blood supply / Q000294:innervation / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C546410:P2rx3 protein, rat; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002211:Capsaicin