Potentiation of ATP-responses at a recombinant P_2X2 receptor by neurotransmitters and related substances

Abstract

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5′-triphosphate (ATP) at a recombinant P_2X2 receptor expressed in defolliculated Xenopus oocytes.

2. Nicotine, 5-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 μM) potentiated the responses to ATP (3 μM), an effect found due to acidification of the bathing solution by these drugs.

3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 μM) and nerve growth factor (NGF; 50 ng ml⁻¹) potentiated the responses to ATP (3 μM) through a largely or wholly pH-independent effect.

4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate.

5. Since P_2X receptors on sensory neurones include P_2X2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.

Full Text

The Full Text of this article is available as a PDF (297.7 KB).