Sympathetic cotransmission of noradrenaline and adenosine triphosphate (ATP) in porcine mesenteric arteries

Amjad Shatarat, William Dunn, Vera Ralevic. University Of Nottingham, Nottingham, United Kingdom.

Background and aims: In the rat perfused mesentery raising the tone with U46619, a thromboxane A2 receptor agonist, enhanced sympathetic nerve mediated responses and increased the importance of ATP as a functional neurotransmitter (Pakdeechote et al., 2007).This study was designed to study sympathetic neurotransmission in porcine mesenteric arteries under raised tone conditions.

Materials and methods: Segments of porcine mesenteric arteries were prepared for isometric tension recording. The segments were preconstricted with U46619 (0.1-1 nM, and the effects of guanethidine (1μM) a sympathetic neurone blocker, prazosin (0.1μM), an α1-adrenoceptor antagonist, α,β-methylene ATP (1μM) a P2X receptor desensitising agent, BIBP3226 (1μM) a NPY Y1 receptor antagonist, and RX 811059 (1μM), an α2-adrenoceptor antagonist were investigated on the contractile response obtained to electrical field stimulation (EFS) (2-16 Hz, 1ms, 90 v, 30 s).

Results and discussion: Guanethidine virtually abolished the response to EFS indicating that the responses were sympathetic in origin. Prazosin significantly attenuated, but did not abolish, the response to EFS (e.g. at 16 Hz:3.7 ± 0.3 g, control, 1.1 ± 0.1 g prazosin, P < 0.001, n = 10, ANOVA followed by Bonferroni post test ) showing that NA is an important sympathetic neurotransmitter acting through α1-adrenoceptors in porcine mesenteric arteries. The presence of either α,β-methylene ATP, BIBP3226 or RX811059 after prazosin, revealed that only α,β-methylene ATP had a significant effect (e.g. at 16 Hz: 3.2±0.28 control, 0.95± 0.11 prazosin, 0.50 ± 0.06 α,β-methylene ATP, P < 0.01, n = 10, ANOVA followed by Bonferroni posttests), indicating that ATP, acting through P2X receptors is involved in mediating part of the responses in porcine mesenteric arteries under raised tone conditions.

Conclusions: this study has shown that NA is the main neurotransmitter acting through α1-adrenoceptor with a contribution of ATP as a cotransmitter acting through P2X receptor in porcine mesenteric arteries under raised tone conditions.

Pakdeechote et al., (2007) J Physiol 582, 745-754