A reevaluation of the mechanisms involved in the secretion of catecholamine evoked by 2,4-dinitrophenol 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 Ca+and Na+ in the extracellular media (Obeso et ai., 1989; Rocher et ai., 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 (OOOso et ai., 1989; Buckler and VaughanJones, 1998). Mitochondrial uncouplers such as DNP, carbonyl cyanide mchlorophenylhydrazone (CCCP) or carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), are protonophores that produce intracellular acidification in several cell types including chemoreceptor cells (Grinstein and Rothstein, 1986; Tretter et ai., 1998; Buckler and Vaughan-Jones, 1998; Park et ai., 2002). An intracellular acidification followed by consecutive activation of Na+/H+ and Na+/Ca+ exchanger was proposed by our group as the mechanism that triggers exocitosis during DNP stimulation in the adult rabbit CB (Rocher et al., 1991 ; Gonzalez et ai., 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