TY - JOUR
T1 - The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body
AU - Fitzgerald, Robert S.
AU - Shirahata, Machiko
AU - Chang, Irene
N1 - Funding Information:
The authors gratefully acknowledge support for this study from the National Institutes of Health, National Heart Lung Blood Institute, specifically awards HL 50712 and HL 61596.
PY - 2009/11/16
Y1 - 2009/11/16
N2 - The carotid body (CB) is a polymodal chemosensor of arterial blood located next to the internal carotid artery. The basic chemosensing unit is composed of the neurotransmitter (NT)-containing glomus cells (GCs) and the sensory afferent fibers synapsing onto the GCs. Nicotinic and muscarinic receptors have been found on both the sensory afferent fibers and on the GCs. Neural output from the CB (CBNO) increases when arterial blood perfusing it is hypoxic, hypoglycemic, hypercapnic, or acidic. The increased CBNO due to GC release of excitatory NTs must be preceded by an entrance of calcium into the GCs. With repeated release of ACh from the GCs, cholinergic receptors could become desensitized, particularly nicotinic receptors which function as calcium channels. The purpose of the present study was to see if adenosine (ADO), known to alter receptor sensitivities, could attenuate or eliminate any desensitization of the nicotinic receptors occurring during the repeated application of ACh. Cat CBs were harvested with techniques approved by the University's Animal Care/Use Committee. The GCs were cultured and prepared for detecting [Ca++]i with standard techniques. Repeated application of ACh produced a progressively decreasing increase in [Ca++]i. With the use of ADO or an A2A ADO receptor agonist the decrease was avoided. Though ADO also increased GC [Ca++]i, the sum of ADO increase and ACh increase, when superfused separately, was less than the increase when they were both included in the same superfusion. This suggested the possible involvement of a new path in the action. Potential mechanisms to explain the phenomena are discussed.
AB - The carotid body (CB) is a polymodal chemosensor of arterial blood located next to the internal carotid artery. The basic chemosensing unit is composed of the neurotransmitter (NT)-containing glomus cells (GCs) and the sensory afferent fibers synapsing onto the GCs. Nicotinic and muscarinic receptors have been found on both the sensory afferent fibers and on the GCs. Neural output from the CB (CBNO) increases when arterial blood perfusing it is hypoxic, hypoglycemic, hypercapnic, or acidic. The increased CBNO due to GC release of excitatory NTs must be preceded by an entrance of calcium into the GCs. With repeated release of ACh from the GCs, cholinergic receptors could become desensitized, particularly nicotinic receptors which function as calcium channels. The purpose of the present study was to see if adenosine (ADO), known to alter receptor sensitivities, could attenuate or eliminate any desensitization of the nicotinic receptors occurring during the repeated application of ACh. Cat CBs were harvested with techniques approved by the University's Animal Care/Use Committee. The GCs were cultured and prepared for detecting [Ca++]i with standard techniques. Repeated application of ACh produced a progressively decreasing increase in [Ca++]i. With the use of ADO or an A2A ADO receptor agonist the decrease was avoided. Though ADO also increased GC [Ca++]i, the sum of ADO increase and ACh increase, when superfused separately, was less than the increase when they were both included in the same superfusion. This suggested the possible involvement of a new path in the action. Potential mechanisms to explain the phenomena are discussed.
KW - ACh
KW - Adenosine
KW - Atropine
KW - Carotid body
KW - Hexamethonium
KW - Intracellular calcium
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U2 - 10.1016/j.brainres.2009.08.100
DO - 10.1016/j.brainres.2009.08.100
M3 - Article
C2 - 19761761
AN - SCOPUS:71849095742
SN - 0006-8993
VL - 1301
SP - 20
EP - 33
JO - Brain research
JF - Brain research
ER -