Effects of Different Types of Stimulation on Cyclic AMP Content in the Rabbit Carotid Body: Functional Significance

Pérez-Garcı́a, M. Teresa; Almaraz, L.; González, C.

doi:10.1111/j.1471-4159.1990.tb03137.x

Cited by 61 publications

(91 citation statements)

References 49 publications

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“…The normoxic cAMP levels do not differ in the four ages studied, and the pattern of cAMP production in response to different O 2 concentrations remained almost unchanged in old animals. The cAMP levels found in the rat CB in the present study, expressed in unit weight, are nearly identical to the values reported in the rabbit CB (Perez-Garcia et al 1990;Chen et al 1997). At all ages, cAMP levels were maximal in normoxic conditions.…”

Section: Discussionsupporting

confidence: 76%

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Monteiro

Batuca

Obeso

et al. 2010

AGE

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The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A 2 -adenosine receptors stimulation and attenuated by D 2 -dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine and dopamine administration is almost unknown. This study aims to investigate the ventilatory response to ischemia and to adenosine, dopamine, and their antagonists in old rats, as well as the effect of hypoxia on adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation in the aged CB. In vivo experiments were performed on young and aged rats anesthetized with pentobarbitone and breathing spontaneously. CB ischemia was induced AGE (2011) 33:337-350 DOI 10.1007 Scientific knowledge on the subject The functional ventilatory consequences of the morphological and molecular changes in the carotid body observed in aged animals, as well as the ventilatory effects of dopamine and adenosine in old animals, are still unknown.What this study adds to the field The carotid body's peripheral control of ventilation is not impaired by aging. The preservation of the inhibitory and excitatory effects on ventilation caused by exogenous dopamine and adenosine, respectively, should be taken into account in the therapeutic use of these amines and their agonists and antagonists in elderly people. by bilateral common carotid occlusions. cAMP content was measured in CB incubated with different oxygen concentrations. Hyperoxia caused a decrease in cAMP in the CB at all ages, but no differences were found between normoxia and hypoxia or between young and old animals. The endogenous dopaminergic inhibitory tonus is slightly reduced. However, both the ventilation decrease caused by exogenous dopamine and the increase mediated by A 2A -adenosine receptors are not impaired in aged animals. The bradycardia induced by adenosine is attenuated in old rats. The CB's peripheral control of ventilation is preserved during aging. Concerns have also arisen regarding the clinical usage of adenosine to revert supraventricular tachycardia and the use of dopamine in critical care situations involving elderly people.

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Section: Discussionsupporting

confidence: 76%

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Monteiro

Batuca

Obeso

et al. 2010

AGE

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“…As we have shown that the effect of adenosine on type I cells is largely Ca¥ independent, as is the hypoxia-induced elevation in cAMP in these cells (Perez-Garcia et al 1990;Wang et al 1991), the simplest explanation for the action of adenosine in type I cells would therefore be via an increase in cAMP. Our data could therefore support the contention of Chen et al (1997) that the elevation of cAMP during hypoxia is mediated by the release of endogenous adenosine.…”

Section: Discussionmentioning

confidence: 93%

Presynaptic action of adenosine on a 4‐aminopyridine‐sensitive current in the rat carotid body

Vandier

Conway

Landauer

et al. 1999

The Journal of Physiology

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1. Plasma adenosine concentration increases during hypoxia to a level that excites carotid body chemoreceptors by an undetermined mechanism. We have examined this further by determining the electrophysiological responses to exogenous adenosine of sinus nerve chemoafferents in vitro and of whole-cell currents in isolated type I cells. 2. Steady-state, single-fibre chemoafferent discharge was increased approximately 5-fold above basal levels by 100 ìÒ adenosine. This adenosine-stimulated discharge was reversibly and increasingly reduced by methoxyverapamil (D600, 100 ìÒ), by application of nickel chloride (Ni¥, 2 mÒ) and by removal of extracellular Ca¥. These effects strongly suggest a presynaptic, excitatory action of adenosine on type I cells of the carotid body. 3. Adenosine decreased whole-cell outward currents at membrane potentials above -40 mV in isolated type I cells recorded during superfusion with bicarbonate-buffered saline solution at 34-36°C. This effect was reversible and concentration dependent with a maximal effect at 10 ìÒ. 4. The degree of current inhibition induced by 10 ìÒ adenosine was voltage independent (45•39 ± 2•55 % (mean ± s.e.m.) between −40 and +30 mV) and largely (•75%), but not entirely, Ca¥ independent. 4-Aminopyridine (4-AP, 5 mÒ) decreased the amplitude of the control outward current by 80•60 ± 3•67 % and abolished the effect of adenosine. 5. Adenosine was without effect upon currents near the resting membrane potential of approximately −55 mV and did not induce depolarization in current-clamp experiments. 6. We conclude that adenosine acts to inhibit a 4-AP-sensitive current in isolated type I cells of the rat carotid body and suggest that this mechanism contributes to the chemoexcitatory effect of adenosine in the whole carotid body.

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“…Since hypoxia causes elevation of cAMP in the carotid body (12)(13)(14), specifically in glomus cells (15), and since cAMP analogs induce Na+ channel expression in PC12 (16) and skeletal muscle (17) cells in vitro, we tested whether the increase in inward current in glomus cells is mimicked by growing normoxic carotid body cultures in the continuous presence of the membrane-permeable cAMP analog Bt2cAMP. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…suggestion that chronic hypoxia over a period of only 2 days resulted in higher resting potentials in glomus cells (23) (12)(13)(14), and specifically in glomus cells (15), the possibility is raised that hypoxia may induce Na+ channels in glomus cells via a cAMP-mediated pathway. It is noteworthy that elevated intracellular cAMP also causes Na+ channel induction in skeletal muscle cells (17) and in the neuroendocrine PC12 cell line (16), whose parental chromaffin cells share several biochemical and ultrastructural similarities with glomus cells (10,20,21) and a common neural crest origin (19).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia and N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, but not nerve growth factor, induce Na+ channels and hypertrophy in chromaffin-like arterial chemoreceptors.

Stea

Jackson

Nurse

1992

Proc. Natl. Acad. Sci. U.S.A.

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Chronic hypoxia sensitizes the ventilatory reflex in mammals and causes enlargement of the carotid body, a peripheral arterial chemosensory organ. To investigate possible underlying mechanisms, in the absence of circulatory changes, we exposed cultures of dissociated rat carotid body containing the oxygen sensors (i.e., chromaffin-like glomus cells) to chronic hypoxia (6% 02) over a period of 2 weeks. After a delay of a few days, the Na+ current density in hypoxia-treated glomus cells increased gn ntly, reaching values up to 6 times that seen in normoxic (20% 02) controls.In addition the whole-cell capacitance, an indicator of cell size, was also significantly larger (3-4 times control) in glomus cells exposed to chronic hypoxia. Both effects were mimicked qualitatively by chronic treatment of normoxic cultures with N6,02-dibutyryladenosine 3',S'-cycic monophosphate, but not nerve growth factor, which is known to induce similar changes in the chromaffm cell line PC12. Thus, the physiological and morphological effects of chronic hypoxia on the carotid body in vivo may be due in part to a cAMP-mediated stimulation of Na+ channel expression and hypertrophy in the chemosensory glomus cells.Conditions of chronic hypoxia, as occur in humans and animals living at high altitude (1) or in patients with hypoxic lung disease (2), cause enlargement or hypertrophy of the carotid body, an organ that senses blood Po2 and controls ventilation. In addition, there is a time-dependent sensitization of this chemosensory pathway (3, 4), resulting in an increased respiratory drive that is thought to be important during acclimatization to hypoxia. The above structural and functional changes may be mediated via a direct action of low arterial Po2 on the carotid-body oxygen sensors (i.e., the chromaffin-like glomus cells), which contain a unique class of 02-sensitive K+ channels (5-7), or indirectly, by way of blood-borne factors arising elsewhere in the circulation. Though there is evidence that the hypertrophic response of the carotid body during chronic hypoxia is accompanied in part by an increased size of the glomus cells (8, 9), the underlying mechanisms associated with the morphological and physiological adaptations of the carotid body to chronic hypoxia are largely unknown. Moreover, these mechanisms are especially difficult to investigate in vivo, where circulatory factors cannot be readily controlled or eliminated.This laboratory has been investigating (7, 10, 11) chemotransduction mechanisms by using dissociated cell cultures of the rat carotid body in which the chemosensory glomus cells survive for several weeks and are accessible for electrophysiological patch-clamp/whole-cell recording. The ability to control the cellular, fluid, and gaseous environments in these cultures allowed us to investigate whether direct exposure ofcarotid body cells alone to chronic hypoxia could alter the physiological and morphological properties of the glomus cells, in the absence of extraneous circulatory factors. In this study, we com...

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Effects of Different Types of Stimulation on Cyclic AMP Content in the Rabbit Carotid Body: Functional Significance

Cited by 61 publications

References 49 publications

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine

Presynaptic action of adenosine on a 4‐aminopyridine‐sensitive current in the rat carotid body

Hypoxia and N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate, but not nerve growth factor, induce Na+ channels and hypertrophy in chromaffin-like arterial chemoreceptors.

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