A Reevaluation of the Mechanisms Involved in the Secretion of Catecholamine Evoked by 2, 4-Dinitro Phenol from Chemoreceptor Cells of the Rabbit Carotid Body
Dinitrophenol (2,4 dinitrophenol; DNP) was early identified as a potent stimulant of the carotid body (CB; Shen and Hauss, 1939). DNP acts directly upon chemoreceptor cells promoting an increase in the intracellular calcium concentration and the release of catecholamine (CA); both responses are strongly dependent on the presence of Ca2+and Na+in the extracellular media (Obesoet al.1989; Rocheret al.1991; Buckler and Vaughan-Jones, 1998). The uncoupling effects of DNP have also been studied in chemoreceptor cells: DNP produces an activation of glucose consumption and a decrease in the mitochondrial membrane potential (Obesoet al.1989; Buckler and Vaughan- Jones, 1998). Mitochondrial uncouplers such as DNP, carbonyl cyanide m-chlorophenylhydrazone (CCCP) or carbonylcyanide p-(trifluoromethoxy)- phenylhydrazone (FCCP), are protonophores that produce intracellular acidification in several cell types including chemoreceptor cells (Grinstein and Rothstein, 1986; Tretteret al.1998; Buckler and Vaughan-Jones, 1998; Parket al.2002). An intracellular acidification followed by consecutive activation of Na+/H+and Na+/Ca2+exchanger was proposed by our group as the mechanism that triggers exocitosis during DNP stimulation in the adult rabbit CB (Rocheret al.1991; Gonzalezet al.1994). In rat neonatal chemoreceptor cells, however, it was found that DNP induces membrane depolarization by inhibiting a background, voltage-insensitive, K+current (Buckler and Vaughan-Jones, 1998). In addition to suppress this current, DNP also activates a yet uncharacterized inward current. In this model, an “unknown link” between DNP-induced mitochondrial depolarization and plasmalemmal K+-channels inhibition was put forward. In this paper, we have restudied the effects of DNP on rabbit chemoreceptor cells looking for the presence in this preparation of membrane depolarization. Results show that the secretion of CA induced by DNP in the rabbit CB is mostly the result of the entry of calcium to the cell via depolarization-activated calcium channels. In the discussion we reevaluate our previous data and hypothesis on the mechanism of DNP stimulation of the CB at the light of our new data. Though the nature of the membrane current targeted by DNP in rabbit CB has not been investigated, our results indicate that in adult rabbit CB chemoreceptor cells operate trough similar mechanisms than in neonatal rat CB chemoreceptor cells.
KeywordsCalcium Channel Carotid Body Membrane Conductance Mitochondrial Uncoupler Intracellular Acidification
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- Shen, TC. and Hauss, WH. (1939). Influence of dinitrophenol, dinitroortocresol and paranitrophenol upon the carotid sinus chemoreceptors of the dog.Arch Int Pharmacodyn Ther63:251–258.Google Scholar