Effect of adenosine on adrenergic neurotransmission and modulation by endothelium in canine pulmonary artery.
To determine the effect of adenosine on adrenergic neurotransmission in pulmonary vasculature and its modulation by endothelial cells, we studied canine pulmonary arteries under isometric conditions in vitro. Adenosine decreased the contractile responses to electrical field stimulation but had no effect on those to norepinephrine. This inhibitory effect was concentration dependent, with a rank order of potency of NECA > 2-chloroadenosine > adenosine >> APNEA (an A3-adenosine-receptor agonist) > CGS-21680 (an A2a agonist) > CCPA (an A1 agonist). Adenosine reduced the electrical field stimulation-evoked 3H overflow in superfused pulmonary artery previously soaked in [3H]norepinephrine. Pretreatment with the adenosine uptake blocker dipyridamole or the adenosine deaminase inhibitor deoxycoformycin enhanced the adenosine action, and this enhancement was not observed in the endothelium-denuded tissues. Adenosine deaminase activity was found in endothelial cells. Therefore, adenosine inhibits norepinephrine release via an A2b-receptor mechanism, an effect that may be modulated by uptake and metabolism by endothelial cells.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Chiyotani
A
A
Takemura
H
H
Nagai
A
A
Konno
K
K
Onuki
T
T
Nitta
S
S
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000294:innervation / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D015649:Pentostatin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D015649:Pentostatin; D004176:Dipyridamole; D000241:Adenosine; D009638:Norepinephrine