Excitatory effect of P2X receptor activation on mesenteric afferent nerves in the anaesthetised rat

• Published in: The Journal of physiology 1999-10, Vol.520 (2), p.551-563
• Main Authors: Kirkup, Anthony J., Booth, Charlotte E., Chessell, Iain P., Humphrey, Patrick P. A.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Blood Pressure - drug effects; Carbolines - pharmacology; Electrophysiology; Heart Rate - drug effects; Jejunum - physiology; Male; Mesentery - innervation; Neurons, Afferent - metabolism; omega-Conotoxins; Original; Peptides - pharmacology; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate - analogs & derivatives; Pyridoxal Phosphate - pharmacology; Rats; Rats, Wistar; Receptors, Purinergic P2 - metabolism; Serotonin - analogs & derivatives; Serotonin - pharmacology; Suramin - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1999.00551.x

We examined the effects of P2X purinoceptor agonists and P2 purinoceptor antagonists on mesenteric afferent nerves supplying the jejunum in the pentobarbitone sodium-anaesthetised rat. ATP (0.01–10 mg kg −1 , i.a. ) and α,β-methylene-ATP (1–30 μg kg −1 , i.a. ) each induced dose-dependent increases in afferent nerve discharge and intrajejunal pressure. The effect on afferent nerves comprised an early (< 2 s after administration) intense burst of activity followed by a later increase (> 2 s after administration), less pronounced in comparison, which coincided with elevated intrajejunal pressure. Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (20 mg kg −1 , i.v. ) and suramin (80 mg kg −1 , i.v. ) each antagonised both the early and later increases in afferent nerve discharge elicited by α,β-methylene-ATP (30 μg kg −1 , i.a. ). Co-administration of ω-conotoxin MVIIA and ω-conotoxin SVIB (each at 25 μg kg −1 , i.v. ), or treatment with the selective 5-HT 3 receptor antagonist alosetron (30 μg kg −1 , i.v. ), did not affect the rapid burst of afferent nerve activity elicited by α,β-methylene-ATP (30 μg kg −1 , i.a. ). However, toxin treatment did attenuate the elevations in intrajejunal pressure and the corresponding later phases of evoked afferent discharge, while alosetron inhibited basal afferent nerve activity. In summary, ATP and α,β-methylene-ATP each evoke excitation of mesenteric afferent nerves in the anaesthetised rat. We propose that the early increase in mesenteric afferent nerve activity represents a direct effect on the nerve ending, mediated by P2X receptors, whereas the later increase reflects activation of mechanosensitive fibres secondary to elevated intrajejunal pressure.