A convenient synthesis of the muscarinic cholinergic antagonist (R)-[N-methyl-3 H]quinuclidinyl benzilate methiodide

2019 ◽  
Vol 62 (9) ◽  
pp. 604-607
Author(s):  
Crist N. Filer ◽  
Richard J. Seguin
Keyword(s):  
Cholinergic Antagonist ◽  
Convenient Synthesis ◽  
Muscarinic Cholinergic ◽  
Quinuclidinyl Benzilate

Isolated parietal cells: [3H]QNB binding to putative cholinergic receptors

1980 ◽  
Vol 239 (3) ◽  
pp. G204-G209
Author(s):  
R. Ecknauer ◽  
W. J. Thompson ◽  
L. R. Johnson ◽  
G. C. Rosenfeld
Keyword(s):  
Specific Binding ◽  
Cholinergic Receptors ◽  
Parietal Cells ◽  
Cholinergic Antagonists ◽  
Single Population ◽  
Muscarinic Cholinergic Receptors ◽  
Cholinergic Antagonist ◽  
Muscarinic Cholinergic ◽  
Quinuclidinyl Benzilate

The tritiated muscarinic cholinergic antagonist quinuclidinyl benzilate, [3H]QNB, was used as a direct probe for the detection and characterization of muscarinic cholinergic receptors associated with the particulate fraction of isolated and purified rat gastric muscosal parietal cells. Specific binding is saturable (Bmax = 55 fmol/mg protein, KD = 0.78 nM), shows a single population of binding sites, and has appropriate pharmacological specificity. Nanomolar concentrations of muscarinic cholinergic antagonists, such as atropine and scopolamine, inhibit [3H]QNB binding by 50%, whereas micromolar concentrations are needed for agonists, such as acetylcholine, oxotremorine, and carbamylcholine. Binding is also stereoselective as shown by the more than 1,000-fold difference in inhibitory potencies of the stereoisomers of benzetimide. Noncholinergic agents, including pentagastrin, histamine, and the H2-receptor antagonists cimetidine and metiamide, have little or no effect on [3H]QNB binding at concentrations of 100 microM. These data support the existence of specific parietal cell muscarinic cholinergic receptors with which the secretagogue acetylcholine may directly interact to initiate gastric acid secretion.

scholarly journals Induction of long-lasting depolarization in medioventral medulla neurons by cholinergic input from the pedunculopontine nucleus

2005 ◽  
Vol 99 (3) ◽  
pp. 1127-1137 ◽  
Author(s):  
Keiko Mamiya ◽  
Kevin Bay ◽  
R. D. Skinner ◽  
E. Garcia-Rill
Keyword(s):  
Action Potential ◽  
Pedunculopontine Nucleus ◽  
Intracellular Recordings ◽  
Stable States ◽  
Cholinergic Agonist ◽  
Firing Rates ◽  
Cholinergic Antagonist ◽  
Muscarinic Cholinergic ◽  
Stimulation Of

Stimulation of the pedunculopontine nucleus (PPN) is known to induce changes in arousal and postural/locomotor states by activation of such descending targets as the caudal pons and the medioventral medulla (MED). Previously, PPN stimulation was reported to induce prolonged responses (PRs) in intracellularly recorded caudal pontine neurons in vitro. The present study used intracellular recordings in semihorizontal slices from rat brain stem (postnatal days 12–21) to determine responses in MED neurons following PPN stimulation. One-half (40/81) of MED neurons showed PRs after PPN stimulation. MED neurons with PRs had shorter duration action potential, longer duration afterhyperpolarization, and higher amplitude afterhyperpolarization than non-PR MED neurons. PR MED neurons were significantly larger (568 ± 44 μm2) than non-PR MED neurons (387 ± 32 μm2). The longest mean duration PRs and maximal firing rates during PRs were induced by PPN stimulation at 60 Hz compared with 10, 30, or 90 Hz. The muscarinic cholinergic agonist carbachol induced depolarization in all PR neurons tested, and the muscarinic cholinergic antagonist scopolamine reduced or blocked carbachol- and PPN stimulation-induced PRs in all MED neurons tested. These findings suggest that PPN stimulation-induced PRs may be due to activation of muscarinic receptor-sensitive channels, allowing MED neurons to respond to a transient, frequency-dependent depolarization with long-lasting stable states. PPN stimulation appears to induce PRs in large MED neurons using parameters known best to induce locomotion.

scholarly journals Global Disturbances in Autonomic Function Yield Cardiovascular Instability and Hypertension in the Chromogranin A Null Mouse

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5027-5035 ◽  
Author(s):  
Jiaur R. Gayen ◽  
Yusu Gu ◽  
Daniel T. O'Connor ◽  
Sushil K. Mahata
Keyword(s):  
Chromogranin A ◽  
Baroreflex Sensitivity ◽  
Autonomic Function ◽  
Plasma Catecholamines ◽  
Conscious State ◽  
Null Mouse ◽  
Wild Type ◽  
Cholinergic Antagonist ◽  
Adrenergic Antagonist ◽  
Muscarinic Cholinergic

We reported previously that chromogranin A (Chga) knockout (KO) mice are hypertensive and hyperadrenergic. Here we sought to determine the basis of such alterations by probing physiological, biochemical, and pharmacological responses to perturbations of the autonomic nervous system. In the conscious state, KO mice had substantially elevated basal high blood pressure (BP) and heart rate (HR); immobilization stress caused increments in systolic BP and HR in both wild-type (WT) and KO mice, with higher maxima but blunted increments in the KO state. Catestatin (CST; CHGA352–372) selectively diminished stress-induced increments in BP and HR in KO mice, implicating CST as an antihypertensive peptide, even in stressful conditions. Heightened plasma catecholamines in KO mice returned to WT level after CST. Stress caused further increments in catecholamines in WT mice but no change in KO mice. KO mice displayed diminished baroreflex sensitivity in response to either phenylephrine or sodium nitroprusside, accounting for exaggerated pressor and depressor responses to these compounds; baroreceptor function was normalized by CST. To probe the relative roles of endogenous/basal sympathetic vs. parasympathetic tone in control of BP and HR, we used the muscarinic-cholinergic antagonist atropine or the β-adrenergic antagonist propranolol; HR and BP responses to each antagonist were exaggerated in KO animals. We conclude that ablation of Chga expression results in global disturbances in autonomic function, both sympathetic and parasympathetic, that can be abrogated (or rescued), at least in part, by replacement of CST. The results point to mechanisms whereby CHGA and its CST fragment act to control cardiovascular homeostasis.

Alpha- and beta-adrenergic and muscarinic cholinergic binding sites in the bladder and urethra of the rabbit

1983 ◽  
Vol 61 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Anthony Johns
Keyword(s):  
Binding Site ◽  
Dissociation Constant ◽  
Receptor Binding ◽  
Binding Sites ◽  
Binding Assays ◽  
Muscarinic Binding Sites ◽  
Rabbit Urethra ◽  
Radioligand Receptor Binding ◽  
Muscarinic Cholinergic ◽  
Quinuclidinyl Benzilate

The affinities of a number of α and β-adrenergic binding sites and muscarinic cholinergic binding sites in rabbit urethra and bladder have been determined, using specific radioligand receptor binding assays. There was a greater density of β-binding sites than α-binding sites in the bladder, while, in the urethra, there was a greater density of α-binding sites than β-binding sites. The number of α-binding sites was fourfold greater in the urethra, whereas there were fewer β-binding sites in the urethra. There were fewer muscarinic binding sites in the urethra than in the bladder. The dissociation constant for [3H]dihydroalprenolol at the β-binding site was 6.4 nM, for [3H]dihydroergocryptine at the α-binding site was 2.11 nM, and for 3H-labelled l-quinuclidinyl benzilate at the muscarinic binding site was 0.22 nM.

Muscarinic Acetycholine Receptors of the Small Intestine and Pancreas of the Rat: Distribution and the Effect of Vagotomy

1982 ◽  
Vol 62 (2) ◽  
pp. 203-207 ◽  
Author(s):  
P. E. T. Isaacs ◽  
J. S. Whitehead ◽  
Y. S. Kim
Keyword(s):  
Small Intestine ◽  
Duodenal Mucosa ◽  
Cholinergic Receptors ◽  
Jejunal Mucosa ◽  
Ileal Mucosa ◽  
Muscarinic Cholinergic Receptors ◽  
Muscarinic Cholinergic ◽  
Small Intestinal ◽  
Mucosal Innervation ◽  
Quinuclidinyl Benzilate

1. The distribution of muscarinic cholinergic receptors (mAChR), detected by atropine-inhibitable binding of [3H]quinuclidinyl benzilate, was examined in membrane fractions of pancreas, small intestinal muscle, mucosa, villi and crypts of sham-operated and vagotomized rats. 2. Specific (atropine inhibitable) [3H]quinuclidinyl benzilate binding was greater to the ileal mucosa than to jejunal mucosa or to duodenal mucosa, but binding to crypt and villus fractions was not significantly different. This distribution of specific [3H]quinuclidinyl benzilate binding suggests that cholinergic mucosal innervation is more important in the ileum than the jejunum. 3. Vagotomy produced a decrease in the amount of specific [3H]quinuclidinyl benzilate binding to duodenal mucosa only, suggesting that parasympathetic denervation of the small intestine does not cause mucosal hypersensitivity to acetylcholine by an increase in mAChR.

Sign in / Sign up

Export Citation Format

Share Document