Release of dopamine and chemoreceptor discharge induced by low pH and high PCO2 stimulation of the cat carotid body.
1. Cat carotid bodies were incubated with the precursor [3H]tyrosine to label the catecholamine deposits and then mounted in a superfusion chamber which allowed simultaneous collection of the released [3H]dopamine (DA) and recording of action potentials from the carotid sinus nerve. 2. Low pH (7.2-6.6) superfusion of the carotid bodies for periods of 10 min produced a parallel increase in the release of [3H]DA and chemoreceptor discharge. 3. Carotid sinus nerve denervation of the carotid body 12-15 days prior to the experiments did not modify the release of [3H]DA elicited by low pH. 4. Superfusion of the carotid bodies with Ca(2+)-free, high-Mg2+ (1.6 mM) media reduced basal release of [3H]DA and chemoreceptor discharge by about 30%. Release evoked by low pH was reduced by 82%. Peak and average chemoreceptor discharge recorded in response to low pH were reduced by 28%. 5. Solutions containing weak acids (sodium acetate, 10 mM), adjusted at pH 7.4, elicited release of [3H]DA and increased chemoreceptor discharge. 6. With HCO3-CO2-buffered superfusion media, a reduction of bicarbonate to 5.6 mM (pH 6.8), an increase in CO2 to 20% (pH 6.8), or a simultaneous increase in CO2 to 20% and bicarbonate to 90 mM (pH 7.4), resulted in all cases in a corresponding increase in [3H]DA release and chemoreceptor discharge. The most effective stimulus was 20% CO2-pH 6.8 and the least effective 5% CO2-5.6 mM-HCO3-pH 6.8. 7. Inhibition of carbonic anhydrase with acetazolamide while perfusing the carotid bodies with a 20% CO2-equilibrated (pH 7.4) solution resulted in comparable reductions in the release of [3H]DA and chemoreceptor discharge. 8. It is concluded that the effective acidic stimulus at the carotid body chemoreceptors is an increase in hydrogen ion concentration in type I cells. It is also concluded that DA plays a critical role in the genesis of carotid sinus nerve discharges.
Rigual
R
R
Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid, Spain.
López-López
J R
JR
Gonzalez
C
C
D000086:Acetazolamide / Q000494:pharmacology; D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials; D000818:Animals; D002245:Carbon Dioxide; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D010477:Perfusion
D002245:Carbon Dioxide; D000086:Acetazolamide; D004298:Dopamine