Activation of P2X receptors for adenosine triphosphate evokes cardiorespiratory reflexes in anaesthetized rats
Article first published online: 22 SEP 2004
The Journal of Physiology
Volume 507, Issue 3, pages 843–855, March 1998
How to Cite
McQueen, D. S., Bond, S. M., Moores, C., Chessell, I., Humphrey, P. P. A. and Dowd, E. (1998), Activation of P2X receptors for adenosine triphosphate evokes cardiorespiratory reflexes in anaesthetized rats. The Journal of Physiology, 507: 843–855. doi: 10.1111/j.1469-7793.1998.843bs.x
- Issue published online: 22 SEP 2004
- Article first published online: 22 SEP 2004
- (Received 9 October 1997; accepted after revision 24 November 1997)
- 1We tested the hypothesis that activation of P2X receptors associated with vagal afferent nerves can evoke a Bezold-Jarisch (B-J) depressor reflex in anaesthetized rats.
- 2Injection of αβ-methylene ATP (αβ-MeATP; 0.6-600 nmol i.v.) evoked a dose-dependent B-J reflex comprising bradycardia, hypotension and apnoea in rats anaesthetized with pentobarbitone. Apnoea was commonly preceded by hyperventilation. Bilateral vagotomy significantly reduced the bradycardia and most of the apnoeic response without affecting hyperventilation, and unmasked a vasopressor response. Hypotension and apnoea were subject to desensitization, and ATP was about 100 times less potent than αβ-MeATP in evoking the B-J reflex.
- 3ED50 values for responses to αβ-MeATP were: bradycardia 14.6 ± 3.8 nmol; apnoea 47.1 ± 8.5 nmol; hyperventilation 23.3 ± 6.0 nmol, n= 14. The ED50 for apnoea was significantly greater than that for bradycardia or hyperventilation (P < 0.05). Atropine (2.8 μmol (kg body wt)−1 i.v.) antagonized the reflex bradycardia and hypotension.
- 4The P2 antagonists suramin (14 μmol (kg body wt)−1 i.v.) and PPADS (17 μmol (kg body wt)−1 i.v.) antagonized the bradycardic and apnoeic components of the reflex response to αβ-MeATP, without reducing the vasopressor or hyperventilatory responses to the agonist.
- 5Recordings from vagal afferents showed that pulmonary inflation receptors were activated by αβ-MeATP in 62 % of units recorded (ED50 22 ± 5 nmol) and this was blocked by PPADS (17 μmol (kg body wt)−1 i.v.); unidentified vagal afferents were also activated.
- 6αβ-MeATP activated carotid chemoreceptor afferents (ED50 23 ± 9 nmol), an action that was unaffected by PPADS or suramin.
- 7The results support the hypothesis that P2X receptor subtypes for ATP are associated with specific sensory nerves that form part of the homeostatic mechanism for cardiovascular and respiratory regulation and these receptors therefore have physiological, pathological and therapeutic significance.