TY - JOUR
T1 - Activation of nicotinic ACh receptors with alpha 4 subunits induces adenosine release at the rat carotid body
AU - Monteiro, Maria Emília Carreira Saraiva
AU - Conde, Silvia Margarida Vilares Santos
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 1 The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. 2 ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. 3 D-Tubocurarine, mecamylamine, DH beta E and alpha-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DH beta E > mecamylamine > D-tubocurarine > alpha-bungarotoxin. 4 The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHbE, a selective nicotinic receptor antagonist. 5 The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. 6 Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with alpha 4 and beta 2 receptor subunits.
AB - 1 The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. 2 ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. 3 D-Tubocurarine, mecamylamine, DH beta E and alpha-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DH beta E > mecamylamine > D-tubocurarine > alpha-bungarotoxin. 4 The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHbE, a selective nicotinic receptor antagonist. 5 The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. 6 Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with alpha 4 and beta 2 receptor subunits.
KW - acetylcholine
KW - RESPIRATION
KW - ACETYLCHOLINE-RECEPTORS
KW - carotid body
KW - nicotinic acetylcholine receptors
KW - chemoreceptors
KW - CHEMORECEPTOR CELLS
KW - DOPAMINE
KW - adenosine
KW - ATP
KW - HYPOXIA
KW - STIMULATION
KW - INFUSION
KW - VENTILATORY RESPONSES
KW - CAT
U2 - 10.1038/sj.bjp.0706676
DO - 10.1038/sj.bjp.0706676
M3 - Article
C2 - 16444287
VL - 147
SP - 783
EP - 789
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 7
ER -