A novel influence of adenosine on ongoing activity in rat rostral ventrolateral medulla

• Published in: Neuroscience Vol. 88; no. 4; pp. 1213 - 1223
• Main Authors: Thomas, T., Spyer, K.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.02.1999; Elsevier
• Subjects: adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; Animals; Antihypertensive Agents - pharmacology; Bicuculline - pharmacology; Biological and medical sciences; cardiovascular; Electric Stimulation; Fundamental and applied biological sciences. Psychology; GABA Antagonists - pharmacology; Hypothalamus - physiology; Male; Medulla Oblongata - cytology; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurons - drug effects; Neurons - physiology; Phenethylamines - pharmacology; Purinergic P1 Receptor Antagonists; rat; Rats; Rats, Sprague-Dawley; rostral ventrolateral medulla; Theophylline - analogs & derivatives; Theophylline - pharmacology; Vertebrates: nervous system and sense organs; Xanthines - pharmacology; adenosine; 8-SPT, 8-sulphophenyltheophylline; rostral ventrolateral medulla; ABP, arterial blood pressure; CPT, cyclopentyl-1,3-dimethylxanthine; HDA, hypothalamic defence area; rat; AN, aortic nerve; cardiovascular; RVLM, rostral ventrolateral medulla; Vertebrata; Adenosine; Cardiovascular control; Mammalia; Rat; Rodentia; Central nervous system; Electrophysiology; Medulla oblongata; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00296-6

We have investigated whether exogenously applied adenosine modulates neuronal activity in a region of the central nervous system crucial for cardiovascular regulation. Extracellular recordings were made from neurons in the rostral ventrolateral medulla of the anaesthetized rat. Ionophoretic application of adenosine altered ongoing activity in 91% of neurons, evoking either a long-lasting depression or a short-lasting increase in firing rate. Both responses were blocked by application of the broad spectrum adenosine receptor antagonist 8-sulphophenyltheophylline, indicating that the responses were mediated by specific cell surface receptors. The adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine blocked the increase, and partially blocked the decrease in firing rate in response to adenosine. The GABA A receptor antagonist bicuculline also blocked the increase in firing rate in response to adenosine suggesting that adenosine may inhibit release of GABA from axon terminals in this region. The adenosine A 2a receptor agonist CGS 21680 produced a long-lasting depression of ongoing activity. These results suggest A 1 receptors mediate an increase in firing rate, whilst A 1 and A 2a receptors mediate decreases in firing rate in some rostral ventrolateral medulla neurons. Thus, adenosine has been shown to modulate the ongoing activity of neurons in the rostral ventrolateral medulla by acting at both A 1 and A 2a receptors. Accordingly we suggest, and provide some evidence to support the idea, that adenosine acts as an important neuromodulator in this region of the central nervous system, possibly by modulating the presynaptic release of neurotransmitters such as GABA.