Journal of Applied Physiology, Vol 59, Issue 5 1428-1433, Copyright © 1985 by American Physiological Society

ARTICLES

Antagonism by theophylline of respiratory inhibition induced by adenosine

F. L. Eldridge, D. E. Millhorn and J. P. Kiley

The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites.

This article has been cited by other articles:

				A. Garcia-Touchard, V. K. Somers, L. J. Olson, and S. M. Caples Central Sleep Apnea: Implications for Congestive Heart Failure Chest, June 1, 2008; 133(6): 1495 - 1504. [Abstract] [Full Text] [PDF]

				M. P. Walsh and J. M. Marshall The role of adenosine in the early respiratory and cardiovascular changes evoked by chronic hypoxia in the rat J. Physiol., August 15, 2006; 575(1): 277 - 289. [Abstract] [Full Text] [PDF]

				N. K. Burki, W. J. Dale, and L.-Y. Lee Intravenous adenosine and dyspnea in humans J Appl Physiol, January 1, 2005; 98(1): 180 - 185. [Abstract] [Full Text] [PDF]

				K. Ballanyi Protective role of neuronal KATP channels in brain hypoxia J. Exp. Biol., August 15, 2004; 207(18): 3201 - 3212. [Abstract] [Full Text] [PDF]

				H. G. Goshgarian Plasticity in Respiratory Motor Control: Invited Review: The crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury J Appl Physiol, February 1, 2003; 94(2): 795 - 810. [Abstract] [Full Text] [PDF]

				H. Nakayama, C. A. Smith, J. R. Rodman, J. B. Skatrud, and J. A. Dempsey Effect of Ventilatory Drive on Carbon Dioxide Sensitivity below Eupnea during Sleep Am. J. Respir. Crit. Care Med., May 1, 2002; 165(9): 1251 - 1260. [Abstract] [Full Text] [PDF]

				B. Wilken, J. M. Ramirez, F. Hanefeld, and D. W. Richter Aminophylline modulation of the mouse respiratory network changes during postnatal maturation J Appl Physiol, November 1, 2000; 89(5): 2015 - 2022. [Abstract] [Full Text] [PDF]

				G. T. Ferguson, N. Khanchandani, C. D. Lattin, and H. G. Goshgarian Clinical Effects of Theophylline on Inspiratory Muscle Drive in Tetraplegia Neurorehabil Neural Repair, September 1, 1999; 13(3): 191 - 197. [Abstract] [PDF]

				S. L. Mironov, K. Langohr, and D. W. Richter A1 Adenosine Receptors Modulate Respiratory Activity of the Neonatal Mouse Via the cAMP-Mediated Signaling Pathway J Neurophysiol, January 1, 1999; 81(1): 247 - 255. [Abstract] [Full Text] [PDF]

				S. Javaheri, T.J. Parker, L. Wexler, J.D. Liming, P. Lindower, and G.A. Roselle Effect of Theophylline on Sleep-Disordered Breathing in Heart Failure N. Engl. J. Med., August 22, 1996; 335(8): 562 - 567. [Abstract] [Full Text] [PDF]