scholarly journals Endothelial muscarinic M3‐receptors: A Σ‐target?

2019 ◽  
Vol 226 (1) ◽  
pp. e13273 ◽  
Author(s):  
Paul M. Vanhoutte
Keyword(s):  
M3 Receptors

Both M1 and M3 receptors regulate exocrine secretion by mucous acini

1996 ◽  
Vol 271 (6) ◽  
pp. C1963-C1972 ◽  
Author(s):  
D. J. Culp ◽  
W. Luo ◽  
L. A. Richardson ◽  
G. E. Watson ◽  
L. R. Latchney
Keyword(s):  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Muscarinic Agonist ◽  
High Affinity ◽  
Muscarinic Response ◽  
M1 Receptor ◽  
M3 Receptors ◽  
Pharmacological Studies ◽  
Equilibrium Dissociation

We investigated the role of M1 and M3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (KB) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (Ki); 1.81 nM] determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found that the M1 receptor antagonist, M1-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M1 and M3 receptors directly regulating mucous acinar exocrine secretion and indicate M3 receptors alone are insufficient to induce a maximal muscarinic response.

Safety and efficacy of mirabegron and solifenacin in elderly patient with overactive bladder

2021 ◽  
Vol 14 (1) ◽  
pp. 53-57
Author(s):  
Tomasz Wiatr ◽  
Piotr Chłosta
Keyword(s):  
Elderly People ◽  
The Elderly ◽  
Similar Efficacy ◽  
Urgency Incontinence ◽  
Bladder Training ◽  
Adrenoceptor Agonist ◽  
Urinary Tract Symptoms ◽  
M3 Receptors ◽  
Lower Urinary

Lower urinary tract symptoms, including urgency, urgency incontinence, pollakiuria and nocturia are common in the elderly people and has significant impact on quality of life. Pharmacological treatment is recommended when conservative management, such as fluid intake normalization or bladder training, does not alleviate symptoms. Antimuscarinics were often used as the I line treatment for OAB, as these drugs block the activity of the muscarinic M2/M3 receptors in the bladder and provide a significant clinical benefit for OAB symptoms in the elderly people, but their side effects are common, often leading to treatment discontinuation. Mirabegron, a β3-adrenoceptor agonist, shows similar efficacy to antimuscarinic drugs without the risk of anticholinergic effects.

Functional subtyping of muscarinic receptors on canine esophageal mucosa

1991 ◽  
Vol 261 (3) ◽  
pp. G464-G469
Author(s):  
R. Lad ◽  
B. Donoff ◽  
P. K. Rangachari
Keyword(s):  
Short Circuit ◽  
Receptor Subtype ◽  
Esophageal Mucosa ◽  
Muscarinic Agonists ◽  
Low Concentrations ◽  
M3 Receptors ◽  
M1 Receptors ◽  
Set Up ◽  
Definition Of

Serosal addition of muscarinic agonists elicited rapid changes in electrical parameters across the isolated canine esophageal epithelium set up in vitro. Both carbachol and the M1-selective agonist, McNeil A343 (McN), increased transmucosal potential differences (PDs), decreased transmucosal resistances (R), and increased short-circuit currents (Isc). Carbachol was more potent and more effective than McN. Muscarinic antagonists were used to define the muscarinic receptor involved. The pA2 values obtained with Schild plots were as follows: atropine 9.14, 4-DAMP 8.98, AFDX-116 6.71, and pirenzepine 7.12. Low concentrations of pirenzepine (10(-8) M), produced a rightward shift in the dose-response curve to McN, without inhibiting responses to carbachol. Thus the receptor subtype is clearly not an M2. As in other glandular systems, M3 receptors are present. Whether M1 receptors also exist requires better definition of receptor densities-reserves in this tissue. Carbachol induced net secretion of Na and Cl and converted a predominantly absorptive tissue to a secretory one.

Involvement of Gαq/11 in the contractile signal transduction pathway of muscarinic M3 receptors in caecal smooth muscle

1996 ◽  
Vol 315 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Pierre Cuq ◽  
Robert Zumbihl ◽  
Thierry Fischer ◽  
Bruno Rouot ◽  
Jean-Pierre Bali ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
M3 Receptors

scholarly journals Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

2017 ◽  
Vol 44 (3) ◽  
pp. 907-919 ◽  
Author(s):  
Qiang Liu ◽  
Deyi Luo ◽  
Tongxin Yang ◽  
Banghua Liao ◽  
Hong Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Structure And Function ◽  
Bladder Function ◽  
Bladder Smooth Muscle ◽  
M3 Receptors ◽  
And Function

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

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