Hypoxia-induced changes in parasympathetic neurochemical markers in guinea pig heart

1981 ◽  
Vol 50 (5) ◽  
pp. 1017-1021 ◽  
Author(s):  
L. H. Crockatt ◽  
D. D. Lund ◽  
P. G. Schmid ◽  
R. Roskoski
Keyword(s):  
Muscarinic Receptor ◽  
Choline Acetyltransferase ◽  
Receptor Density ◽  
Parasympathetic Innervation ◽  
Guinea Pig Heart ◽  
Receptor Number ◽  
Muscarinic Cholinergic ◽  
Induced Changes ◽  
Neurochemical Marker ◽  
Quinuclidinyl Benzilate

Exposure of animals to hypoxia produces cardiovascular changes including right ventricular hypertrophy and alterations in heart rate. The activity of choline acetyltransferase, a neurochemical marker of parasympathetic innervation, and the density of muscarinic cholinergic receptors, measured by the binding of [3H]quinuclidinyl benzilate, were analyzed in the hearts of guinea pigs exposed to hypobaric hypoxia. We found a significant increase in the activity of choline acetyltransferase in the sinoatrial node in response to hypoxia after 7 or 14 days. In addition, we found significant decreases in the muscarinic receptor density in several contractile and conducting regions. The decrease in receptor density may reflect regulation by the level of occupancy; an increased occupancy may produce a decrease in muscarinic receptor number.

Influence of chronic oestrogen treatment on the density of muscarinic cholinergic receptors and calcium channels in the rabbit uterus

1990 ◽  
Vol 125 (2) ◽  
pp. 185-189 ◽  
Author(s):  
S. Batra
Keyword(s):  
Muscarinic Receptor ◽  
Binding Sites ◽  
Contractile Response ◽  
Receptor Density ◽  
Uterine Weight ◽  
Muscarinic Cholinergic Receptors ◽  
Oestrogen Treatment ◽  
Receptor Affinity ◽  
Wet Weight ◽  
Muscarinic Cholinergic

ABSTRACT Ovariectomized rabbits were treated for 1 or 8 weeks with oestrogen and the effects on uterine weight, muscarinic receptor density and nitrendipine-binding sites on myometrial membranes were studied. The wet weight of the uterus after 1 week of oestrogen treatment increased more than tenfold and increased further by approximately 50% after 8 weeks of oestrogen treatment. The muscarinic receptor density increased significantly after 1 week of oestrogen treatment. Although there was no further increase in receptor density with continuing oestrogen treatment up to 8 weeks, the muscarinic receptor affinity increased significantly. The density of nitrendipine-binding sites increased sixfold after 1 week of oestrogen treatment and did not change thereafter. Oestrogen treatment had no influence on the affinity of nitrendipine-binding sites. The increase by oestrogen in muscarinic receptor density and in nitrendipine-binding sites as shown by the present data is consistent with the generally reported increase in agonist-induced contractile response of the myometrium following oestrogen treatment. Journal of Endocrinology (1990) 125, 185–189

Exercise training alters the effect of chronic hypoxia on myocardial adrenergic and muscarinic receptor number

2001 ◽  
Vol 91 (3) ◽  
pp. 1283-1288 ◽  
Author(s):  
Fabrice Favret ◽  
Kyle K. Henderson ◽  
Richard L. Clancy ◽  
Jean-Paul Richalet ◽  
Norberto C. Gonzalez
Keyword(s):  
Exercise Training ◽  
Muscarinic Receptor ◽  
Sympathetic Activity ◽  
Receptor Expression ◽  
The Other ◽  
Hypoxic Exposure ◽  
Receptor Density ◽  
Other Hand ◽  
Receptor Number ◽  
And Training

Chronic hypoxic exposure results in elevated sympathetic activity leading to downregulation of myocardial α1- and β-adrenoceptors (α1-AR, β-AR). On the other hand, it has been shown that sympathetic activity is reduced by exercise training. The objective of this study was to determine whether exercise training could modify the changes in receptor expression associated with acclimatization. Four groups of rats were studied: normoxic sedentary rats (NS), rats living and training in normoxia (NTN), sedentary rats living in hypoxia (HS, inspired Po 2 = 110 Torr), and rats living and training in hypoxia (HTH, inspired Po 2 = 110 Torr). Training consisted of running in a treadmill at 80% of maximal O2 uptake during 10 wk. Myocardial receptor density was measured by radioactive ligand binding. Right ventricular (RV) hypertrophy occurred in HS but not in HTH. No effect of exercise was detected in RV weight of normoxic rats. Acclimatization to hypoxia (HS vs. NS) resulted in a decrease in both α1- and β-AR density, whereas muscarinic receptor (M-Ach) expression increased. Hypoxic exercise training (HS vs. HTH) moderated β-AR downregulation and M-Ach upregulation and prevented the fall in α1-AR density. Normoxic training (NS vs. NTN) did not change β-AR density. On the other hand, densities of α1-AR in both ventricles as well as RV M-Ach increased in NTN vs. NS. The data show that exercise training in hypoxia 1) prevents RV hypertrophy, 2) suppresses the downregulation of α1-AR in the left ventricle (LV) and RV, and 3) attenuates the changes in both β-AR and M-Ach receptor density in LV and RV. Exercise training in normoxia increases M-Ach receptor expression in the RV.

Increased Myocardial Muscarinic Receptor Density in Idiopathic Dilated Cardiomyopathy

Circulation ◽  
1997 ◽  
Vol 96 (10) ◽  
pp. 3416-3422 ◽  
Author(s):  
Dominique Le Guludec ◽  
Alain Cohen-Solal ◽  
Jacques Delforge ◽  
Nicolas Delahaye ◽  
André Syrota ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Muscarinic Receptor ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Receptor Density

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion

1992 ◽  
Vol 262 (2) ◽  
pp. L223-L228 ◽  
Author(s):  
H. Ishihara ◽  
S. Shimura ◽  
M. Satoh ◽  
T. Masuda ◽  
H. Nonaka ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Gland Secretion ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Submucosal Gland ◽  
Muscarinic Receptor Subtypes ◽  
Binding Assays ◽  
Submucosal Glands ◽  
Electrolyte Secretion ◽  
Quinuclidinyl Benzilate

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Tyrosine hydroxylase and choline acetyltransferase activities in ischemic canine heart

1982 ◽  
Vol 243 (5) ◽  
pp. H788-H795 ◽  
Author(s):  
P. G. Schmid ◽  
B. J. Greif ◽  
D. D. Lund ◽  
R. Roskoski
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Tyrosine Hydroxylase ◽  
Choline Acetyltransferase ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Canine Heart ◽  
Parasympathetic Innervation ◽  
Ischemic Tissue ◽  
Biochemical Indices

After coronary artery occlusion, enzymes involved in the synthesis of sympathetic and parasympathetic neurotransmitters may change disparately. We investigated this in the canine heart by measuring the activity of tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) in normal and ischemic tissue. Myocardial blood flow in selected regions was measured by the microsphere technique. Dogs had either ligation of the anterior descending coronary artery (LAD) or sham ligation (S). In the ischemic zone 5 h after LAD ligation, TH activity was lower than in corresponding anterior apical zones of S dogs (5.1 +/- 1.7 vs. 13.5 +/- 2.3 nmol.g-1.h-1) (P less than 0.05) with a tendency for greater decreases in endocardium than in epicardium. In contrast, there were insignificant changes in CAT activity 2.5 and 5 h after LAD ligation. Thereafter, progressive and significant (P less than 0.05) decreases occurred in CAT activity at 25 and 170 h after LAD ligation. Thus there are early heterogeneous decreases in TH activity that correlate directly with heterogeneous deficits in blood flow. Although decreases in CAT are also heterogeneous and correlate with deficits in perfusion, these changes occur later. These results indicate differences in the effects of infarction on these biochemical indices of sympathetic and parasympathetic innervation in canine heart.

Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart

1993 ◽  
Vol 75 (3) ◽  
pp. 1123-1128 ◽  
Author(s):  
R. Kacimi ◽  
J. P. Richalet ◽  
B. Crozatier
Keyword(s):  
Chronic Hypoxia ◽  
Dissociation Constants ◽  
Receptor Density ◽  
Differential Modulation ◽  
Chronotropic Response ◽  
Constant Displacement ◽  
A1 Receptor ◽  
Muscarinic M2 Receptors ◽  
Cardiac Receptors ◽  
Quinuclidinyl Benzilate

To better understand the decreased chronotropic response to catecholamines in chronic hypoxia, we compared the inhibitory pathways regulating adenylate cyclase in rats exposed for 30 days to hypobaric hypoxia (380 Torr; HX) with those in control rats (CT) by the analysis of adenosinergic A1-receptors (8-cyclopentyl-1,3-[3H]dipropylxanthine) and muscarinic M2-receptors ([3H]quinuclidinyl benzilate). A1-receptor density was decreased by 46% in sarcolemmal preparations without a change in the affinity for agonist [(R)-phenylisopropyladenosine]. M2-receptor density was increased (HX: 280 +/- 16 fmol/mg, CT: 188 +/- 15 fmol/mg; n = 7; P < 0.001) without a change in dissociation constant. Displacement of [3H]quinuclidinyl benzilate by carbachol indicated significant decreases in the dissociation constants of both superhigh- (HX: 73 +/- 19 nM, CT: 182 +/- 42 nM; P < 0.001) and high-affinity binding sites (HX: 4 +/- 1 microM, CT: 12 +/- 3 microM; P < 0.001). Our data show that chronic hypoxia leads to differential modulation of cardiac receptors with a downregulation of adenosine receptors and increases in muscarinic receptor affinity and density, which may contribute to the blunted responsiveness of the heart to catecholamines.

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