Dependence of carotid chemosensory responses on metabolic substrates.
The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusate flow interruption) were measured (n = 33 carotid bodies). The response to nicotine (n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption (n = 4) and nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate without lactic acid production, O2 chemoreception does not depend on lactic acidosis.
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104.
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Spergel
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Lahiri
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Wilson
D000596:Amino Acids / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002344:Carotid Body / Q000378:metabolism / Q000503:physiopathology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D009538:Nicotine / Q000494:pharmacology; D010477:Perfusion / Q000379:methods
D000596:Amino Acids; D001786:Blood Glucose; D005971:Glutamates; D018698:Glutamic Acid; D009538:Nicotine; D005947:Glucose