ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents

Area of Science:

• Physiology
• Neuroscience
• Pharmacology

Background:

• Adenosine triphosphate (ATP) is a key signaling molecule in various physiological processes.
• Purinergic receptors, including P2X and P2Y subtypes, mediate ATP's effects.
• The role of P2X purinoceptors in cardiovascular regulation, particularly in skeletal muscle, requires further elucidation.

Purpose of the Study:

• To investigate the effect of P2X purinoceptor stimulation on blood pressure in decerebrate cats.
• To determine if ATP acting via P2X receptors sensitizes muscle afferents, thereby augmenting the pressor response to muscle stretch.

Main Methods:

• Administration of alpha,beta-methylene ATP (a P2X agonist) via femoral artery injection in decerebrate cats.
• Assessment of mean arterial pressure (MAP) changes in response to varying doses of the agonist.
• Utilized P2X and P2Y receptor antagonists (pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid and reactive blue 2, respectively) to identify receptor involvement.
• Investigated the effect of ATP and alpha,beta-methylene ATP on MAP response to controlled muscle stretch, with and without P1 and P2X receptor antagonists.

Main Results:

• Intra-arterial injection of alpha,beta-methylene ATP caused a dose-dependent increase in MAP.
• The P2X receptor antagonist significantly attenuated the pressor response to alpha,beta-methylene ATP, while the P2Y antagonist had no effect.
• ATP and alpha,beta-methylene ATP pre-treatment enhanced the pressor response to muscle stretch.
• This enhancement was blocked by the P2X antagonist but not by the P1 antagonist.

Conclusions:

• Activation of skeletal muscle P2X purinoceptors by ATP elicits a pressor response mediated by muscle afferents.
• ATP sensitizes muscle afferents through P2X receptors, leading to an augmented blood pressure response during muscle stretch.