Chronic Sympathectomy of Canine Cardiac Ventricles Affects Gs-Adenylyl Cyclase Coupling and Muscarinic Receptor Density

Quist, Eugene E.; Lee, Shang Chiun; Vasan, Ranga; Foresman, Brian H.; Gwirtz, Patricia A.; Jones, C. E.

doi:10.1097/00005344-199406000-00012

Cited by 8 publications

(4 citation statements)

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“…This hypothesis has been tested using chemical sympathectomy with 6-hydroxydopamine and demonstrated no change in fi~-ars in the SA node, AV conducting system, and myocardium, and no change in the pattern of receptor loss with (-)-isoprenaline infusion (Kompa et al 1995). Similar findings have been reported following chronic sympathectomy of canine ventricle (Quist et al 1994). There are also intrinsic differences between the /~-and fi2-ar proteins in susceptibility to phosphorylation and desensitisation.…”

Section: Discussionmentioning

confidence: 73%

Chronic (?)-isoprenaline infusion down-regulates ?1- and ?2-adrenoceptors but does not transregulate muscarinic cholinoceptors in rat heart

Matthews

Falckh

Molenaar

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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Regulation of beta-adrenoceptor (beta-ar) subtypes and transregulation of muscarinic cholinoceptors (mAchr) was examined in regions of rat heart after chronic infusion of (-)-isoprenaline (450 micrograms/kg per hour) for 14 days. Following (-)-isoprenaline infusion systolic blood pressure was reduced for 10 days but then gradually returned to control levels, whereas heart rate was increased for 7 days before declining to a level significantly above control. Heart weight to body weight ratio was increased in (-)-isoprenaline treated rats. beta-ar subtype densities were measured by quantitative autoradiography with [125I]-cyanopindolol (CYP) in sinoatrial node (SA), atrioventricular node (AV), bundle of His (BH), left (LB) and right (RB) bundle branches, interventricular (IVS) and interatrial (IAS) septa, right atria (RA), apex (AX) and mitral valve (MV). beta 1-ars were reduced by 59.1-74.2% in the AV conducting regions, 53.4% in the SA node and 43.3-53.4% in myocardial areas, beta 2-ars were markedly reduced in myocardial regions (93.2-98.5%) and in pacemaker and conducting regions (87.7-97.8%). No changes in mAchr densities measured using [3H]-N-methyl scopolamine (NMS) occurred in the AV node, BH, LB, RB, IVS and IAS following (-)-isoprenaline infusion. Densities of beta 1- and beta 2-ars and mAchrs were also measured in ventricular homogenates from control and (-)-isoprenaline treated animals. beta-ar levels were significantly reduced (P < 0.05) in treated animals and the ratio of beta 1- to beta 2-ars increased after treatment. mAchr density in ventricular homogenates measured using either [3H]-NMS or [3H]-quinuclidinyl [phenyl-4-3H]benzilate (QNB) was unchanged. Homogenates of left and right ventricle also showed no change using [3H]-NMS. Organ bath studies were used to investigate the effect of (-)-isoprenaline infusion on negative inotropic and chronotropic effects of the non-selective muscarinic receptor agonist bethanechol in left and right atria, respectively. Lower concentrations of bethanechol (3 x 10(-10) to 10(-6) M) produced a negative inotropic response in isolated electrically driven left atria from (-)-isoprenaline treated rats, but not from control rats, with the slope of the curves being significantly different between groups (ANCOVA, P = 0.037). At concentrations of bethanechol from 10(-6) to 3 x 10(-4) M the negative inotropic response was not changed between (-)-isoprenaline treated and control animals. Bethanechol also produced a negative chronotropic response at lower concentrations (10(-10) to 10(-6) M) in (-)-isoprenaline treated rats, but not in controls. A second, steeper phase of the negative chronotropic response occurred at concentrations of bethanechol greater than 10(-6) M and was also seen in control rats. Expression of M2 (cardiac) mAchrs (m2Achr) in left and right ventricular tissues measured using a quantitative non-competitive polymerase chain reaction (PCR) assay showed a significant (P = 0.001) 28.5% increase in expression in left ventricle and a significant (P = 0.003) 21...

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Section: Discussionmentioning

confidence: 73%

Chronic (?)-isoprenaline infusion down-regulates ?1- and ?2-adrenoceptors but does not transregulate muscarinic cholinoceptors in rat heart

Matthews

Falckh

Molenaar

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…After drying the filters and adding the scintillation fluid (Rotiszint 11, Roth, Karlsruhe, Germany), the radioactivity was measured using a Wallac Scintillation Counter (Perkin-Elmer Life Sciences) at counting efficiency of ∼50%. Nonspecific binding was defined as [ 3 H]NMS binding at various concentrations which could not be displaced by a high concentration of the non-selective muscarinic receptor antagonist atropine (1 μmol/L; Quist et al (1994)). Specific binding of [ 3 H]NMS was defined as total binding minus non-specific binding, and was 80-90% (at 0.1-3 nmol/L) and 70% (at 10 nmol/L) of [ 3 H]NMS, except in the lung.…”

Section: Receptor Binding Assaysmentioning

confidence: 99%

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Abraham

Kottke

Ammer³

et al. 2006

Vet Res Commun

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Muscarinic receptors are considered to be of comparable clinical importance in chronic obstructive pulmonary disease (COPD) in equines and in humans. At present, data are scarce on the expression and distribution of probable subtypes of these receptors and their signalling pathways in airway segments, including lung parenchyma and bronchial and tracheal epithelium with the underlying smooth muscle in horses. Specific [N-methyl-3H]scopolamine chloride ([3H]NMS) binding to all three tissues was saturable and of high affinity, with KD values ranging between 1.6+/-0.7 and 1.9+/-0.3 nmol/L. [3H]NMS binding identified a higher density of total muscarinic receptors (fmol/mg protein) in the trachea (720+/-59 nmol/L) than in bronchi (438+/-48 nmol/L) or lung (22 +/- 3 nmol/L). Competitive binding studies using [3H]NMS and the unlabelled subtype-selective antagonists pirenzepine and telenzepine (M1), methoctramine and himbacine (M2), 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3), tropicamide (M4) and mamba toxin (MT-3) (M4) indicated the presence of at least three muscarinic receptor subtypes in peripheral lung tissue (50:40:24-28%: M2>M3>M1), whereas in bronchus and trachea M2 subtypes (87-90%) predominated over M3 (14-22%), and M1 subtypes were lacking. No differences were found between tissues in high-affinity binding sites for carbachol in the absence (31-36%) or presence of guanosine 5'-triphosphate (GTP) (approximately 100%). Western blotting for G-protein alpha-subunits showed a much more robust expression of G(alphai1/2) in the trachea (with highest receptor density) than in the lung or bronchi, whereas G(alphas)-protein was dominantly expressed in bronchus. Concomitantly, carbachol inhibited isoproterenol- and GTP-stimulated adenylyl cyclase activity with increasing muscarinic receptor expression (trachea > bronchi > lung). We conclude that the expression and signalling pathways of muscarinic receptors in the equine respiratory tract are segment-dependent. These receptors might contribute to the pathogenesis of COPD in the horse and could provide potential drug targets for the therapeutic use of anticholinergics in this species.

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“…The muscarinic receptor subtype distribution was determined in turkey cardiac chamber membranes by displacing 2 nM of [ 3 H]-NMS with increasing concentrations (10 −10 –10 −4 M) of different nonlabeled selective antagonists (M 1 , M 2 , or M 3 ) and atropine as a nonselective muscarinic receptor antagonist ( Quist et al, 1994 ) as recently described by Schoeller et al (2021) . Pirenzepine was used to identify the M 1 -subtype ( Watson et al, 1983 ); methoctramine for M 2 subtype ( van Zwieten and Doods, 1995 ), 4-DAMP (4-diphenylacetoxy-N-methyl piperidine methiodide) for M 3 subtype ( Michel and Whiting, 1989 ); Tropicamide ( Lazareno and Birdsall, 1993 ) specific for M 4 subtype.…”

Section: Methodsmentioning

confidence: 99%

Assessing the effect of breed, age, and sex on muscarinic receptor distribution in atria and ventricles of turkeys

Schoeller,

Abraham

2024

Poultry Science

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Chronic Sympathectomy of Canine Cardiac Ventricles Affects Gs-Adenylyl Cyclase Coupling and Muscarinic Receptor Density

Cited by 8 publications

References 0 publications

Chronic (?)-isoprenaline infusion down-regulates ?1- and ?2-adrenoceptors but does not transregulate muscarinic cholinoceptors in rat heart

Chronic (?)-isoprenaline infusion down-regulates ?1- and ?2-adrenoceptors but does not transregulate muscarinic cholinoceptors in rat heart

Segment-dependent Expression of Muscarinic Acetylcholine Receptors and G-protein Coupling in the Equine Respiratory Tract

Assessing the effect of breed, age, and sex on muscarinic receptor distribution in atria and ventricles of turkeys

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