ATP stimulates peripheral axons in human, rat and mouse--differential involvement of A(2B) adenosine and P2X purinergic receptors.
Receptors for ATP have been reported on peripheral nerve terminals. It is a widespread assumption that the axonal membrane does not possess this kind of chemosensitivity, although P2X purinoceptors have been found in isolated rat vagus nerve. Therefore, in the present study, effects of ATP and analogues were tested on the excitability of unmyelinated axons in isolated rat sural nerve, mouse dorsal roots, and human sural nerve. Bath application of ATP to all three types of axonal preparations increased axonal excitability, but the underlying receptors appear to differ in the various preparations. In rat sural nerve, alpha,beta-adenosine-5'-methylene triphosphate produced the strongest excitation. This effect was blocked by pyridoxal-phosphate-6-azophenyl-2',5'-disulphonic acid and indicates the presence of P2X receptors. In mouse dorsal roots, differences were found between fast and slow C-fibres. The latter responded to both P2X receptor and adenosine receptor agonists. In contrast, effects of ATP on faster-conducting C-fibres seem to be caused exclusively by effects of ATP on adenosine receptors. Application of ATP also excited C-fibres in fascicles of isolated human nerve. The pharmacological profile indicates activation of A(2B) adenosine receptors. However, we could not detect P2X receptors in this preparation with our techniques. These data show that the ATP sensitivity of sensory neurones is not restricted to their terminals. Activation of axonal purinergic receptors may contribute to the transduction of sensory, including nociceptive, stimuli.
Irnich
D
D
Institute of Physiology, University of Munich, Pettenkoferstrasse 12, D-80336 Munich, Germany.
Tracey
D J
DJ
Polten
J
J
Burgstahler
R
R
Grafe
P
P
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013497:Sural Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate