Central A1-receptor activation associated with onset of torpor protects the heart against low temperature in the Syrian hamster

2008 ◽  
Vol 295 (3) ◽  
pp. R991-R996 ◽  
Author(s):  
Seiji Miyazawa ◽  
Yasutake Shimizu ◽  
Takahiko Shiina ◽  
Haruko Hirayama ◽  
Hironobu Morita ◽  
...  
Keyword(s):  
Body Temperature ◽  
Low Temperature ◽  
Receptor Activation ◽  
Central Administration ◽  
Crucial Effect ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Specific Reactions ◽  
Irreversible Injury ◽  
Hypothermic Condition

Body temperature drops dramatically during hibernation, but the heart retains the ability to contract and is resistant to induction of arrhythmia. Although adaptive changes in the heart prior to hibernation may be involved in the cold-resistant property, it remains unclear whether these changes are sufficient for maintaining cardiac pulsatility under an extreme hypothermic condition. We forcibly induced hypothermia in Syrian hamsters by pentobarbital anesthesia combined with cooling of the animals. This allows reproduction of a hypothermic condition in the absence of possible hibernation-specific reactions. Unlike hypothermia in natural hibernation, the forced induction of hypothermia caused atrioventricular block. Furthermore, J-waves, which are typically observed during hypothermia in nonhibernators, were recorded on an ECG. The origin of the J-wave seemed to be related to irreversible injury of the myocardium, because J-waves remained after recovery of body temperature. An abnormal ECG was also found when hypothermia was induced in hamsters that were well adapted to a cold and darkened environment or hamsters that had already experienced hibernation. These results suggest that acclimatization prior to hibernation does not have a crucial effect at least on acquisition of cardiac resistance to low temperature. In contrast, an abnormal ECG was not observed in the case of hypothermia induced by central administration of an adenosine A1-receptor agonist and subsequent cooling, confirming the importance of the adenosine system for inducing hibernation. Our results suggest that some specific mechanisms, which may be driven by a central adenosine system, operate for maintaining the proper cardiac pulsatility under extreme hypothermia.

Regulation of Na(+)-3HCO3- cotransport in rabbit proximal convoluted tubule via adenosine A1 receptor

1993 ◽  
Vol 265 (4) ◽  
pp. F511-F519 ◽  
Author(s):  
M. Takeda ◽  
K. Yoshitomi ◽  
M. Imai
Keyword(s):  
Basolateral Membrane ◽  
Receptor Activation ◽  
Proximal Convoluted Tubule ◽  
Adenosine A1 Receptor ◽  
Intracellular Camp ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Adenosine A1 ◽  
A1 Receptor

We investigated the role of adenosine A1-receptor in the regulation of basolateral Na(+)-3HCO3- cotransporter in the rabbit proximal convoluted tubule (PCT) microperfused in vitro by monitoring basolateral membrane potential and intracellular pH. FK-453, a highly specific A1 antagonist, inhibited basolateral HCO3- conductance in a concentration-dependent manner (10(-10)-10(-5) M). Other A1 antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-5) M and theophylline at 10(-3) M, also had similar effects. N6-cyclohexyladenosine (CHA) at 10(-7) M attenuated the effect of low concentration (10(-8) M) of FK-453. Either enhancement of the degradation of adenosine by 0.1 U/ml adenosine deaminase (ADA) or inhibition of adenosine release from the cells by 10(-6) M S-(4-nitrobenzyl)-6-thioinosine (NBTI) mimicked the effects of A1 antagonists. These observations suggest that endogenous adenosine is released from PCT cells and stimulates Na(+)-3HCO3- cotransporter. Both 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) and 10(-6) M forskolin also inhibited basolateral HCO3- conductance. Both 10(-6) M FK-453 and 10(-4) M CPT-cAMP decreased the initial rate as well as the magnitude of intracellular acidification induced by reduction of peritubular HCO3- concentration from 25 to 0 mM. Neither 10(-6) M FK-453 nor 10(-7) M CHA changed intracellular Ca2+ concentration as measured by fura-2 fluorescence. These results indicate that adenosine might stimulate HCO3- exit across the basolateral membrane through Na(+)-3HCO3- cotransporter by decreasing intracellular cAMP via A1-receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of ATP-sensitive K+ channels in rabbit ventricular myocytes by adenosine A1 receptor activation

1997 ◽  
Vol 272 (1) ◽  
pp. H325-H333 ◽  
Author(s):  
E. Kim ◽  
J. Han ◽  
W. Ho ◽  
Y. E. Earm
Keyword(s):  
Katp Channel ◽  
Ventricular Myocytes ◽  
Receptor Activation ◽  
Adenosine A1 Receptor ◽  
Channel Activity ◽  
Patch Clamp Technique ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Channel Analysis ◽  
Rabbit Ventricular Myocytes

The objective of the present study was to characterize the role of adenosine in the regulation of ATP-sensitive K (KATP) channel activity in isolated rabbit ventricular myocytes using the patch-clamp technique. In an outside-out patch exposed to guanosine 5'-triphosphate and ATP at the intracellular surface, external adenosine stimulated KATP channel activity. In an inside-out patch exposed to external adenosine, ATP reduced KATP channel activity and guanosine 5'-triphosphate stimulated KATP channel activity. Guanosine 5'-O-(3-thiotriphosphate) resulted in a gradual increase of KATP channel activity even in the absence of adenosine. When myocytes were preincubated with pertussis toxin or 8-cyclopentyl-1,3-dipropylxanthine, adenosine A1 receptor activation failed to activate the KATP channel. Analysis of the open and closed time distributions showed that adenosine A1 receptor activation increased burst duration and decreased interburst duration. In a dose-response relationship for ATP, adenosine A1 receptor activation shifted the half-maximal inhibition of the KATP channel from 70 to 241 microM.

scholarly journals Influence of β-adrenoceptor tone on the cardioprotective efficacy of adenosine A1 receptor activation in isolated working rat hearts

2000 ◽  
Vol 131 (3) ◽  
pp. 537-545 ◽  
Author(s):  
William R Ford ◽  
Bodh I Jugdutt ◽  
Gary D Lopaschuk ◽  
Rick Schulz ◽  
Alexander S Clanachan
Keyword(s):  
Receptor Activation ◽  
Adenosine A1 Receptor ◽  
Rat Hearts ◽  
Adenosine A1 ◽  
A1 Receptor

scholarly journals Adenosine A1 Receptors in Mouse Pontine Reticular Formation Depress Breathing, Increase Anesthesia Recovery Time, and Decrease Acetylcholine Release

2013 ◽  
Vol 118 (2) ◽  
pp. 327-336 ◽  
Author(s):  
George C. Gettys ◽  
Fang Liu ◽  
Ed Kimlin ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Reticular Formation ◽  
Acetylcholine Release ◽  
Adenosine A1 Receptor ◽  
Breathing Rate ◽  
Pontine Reticular Formation ◽  
Central Administration ◽  
Behavioral Arousal ◽  
Adenosine A1 Receptors ◽  
Adenosine A1 ◽  
A1 Receptor

Abstract Background: Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Methods: Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N6-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8-cyclopentylxanthine. Results: First, SPA significantly decreased respiratory rate (−18%), tidal volume (−12%), and minute ventilation (−16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Conclusions: Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

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