Activation of nicotinic ACh receptors with alpha4 subunits induces adenosine release at the rat carotid body.
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. 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. D-Tubocurarine, mecamylamine, DHbetaE 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 DHbetaE>mecamylamine>D-tubocurarine>alpha-bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHbetaE, a selective nicotinic receptor antagonist. The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. 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 alpha4 and beta2 receptor subunits.
Conde
Sílvia V
SV
Department of Pharmacology, Faculty of Medical Sciences, New University of Lisbon, Campo Mártires da Pátria, 130, Lisbon 1169-056, Portugal.
Monteiro
Emília C
EC
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects*
D000241:Adenosine; D000255:Adenosine Triphosphate; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009711:Nucleotides; D011978:Receptors, Nicotinic