Related Experiment Video
Updated: Jul 19, 2026
10:26
Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
Smooth muscle cholinergic denervation hypersensitivity in diverticular disease
Mark Golder1, David E Burleigh, Abi Belai
1Academic Department of Surgery, Barts and The London School of Medicine and Dentistry, Whitechapel, London, UK. m.s.golder@qmul.ac.uk <m.s.golder@qmul.ac.uk>
Lancet (London, England)
|June 13, 2003
Summary
Diverticular disease is linked to reduced neural cholinergic activity and increased smooth muscle M3 receptors. This suggests cholinergic denervation hypersensitivity may explain disease abnormalities.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Smooth Muscle Physiology
Background:
- Diverticular disease pathogenesis may involve cholinergic system disturbances.
- The precise mechanisms of cholinergic involvement remain unclear.
- Investigating smooth muscle and neural cholinergic activity is crucial.
Purpose of the Study:
- To investigate the role of smooth muscle and neural cholinergic activity in diverticular disease.
- To determine if cholinergic denervation hypersensitivity is present in diverticular disease.
Main Methods:
- Immunohistochemical analysis of choline acetyltransferase and M3 receptors in sigmoid colon tissues from patients and controls.
- Organ bath experiments to assess acetylcholine sensitivity in muscle strips.
Main Results:
- Lower choline acetyltransferase activity in both circular and longitudinal smooth muscle of patients with diverticular disease.
- Upregulated M3 receptors in the smooth muscle of patients with diverticular disease.
- Increased sensitivity to acetylcholine in circular muscle, but not longitudinal muscle, of patients with diverticular disease.
Conclusions:
- Results suggest cholinergic denervation hypersensitivity in smooth muscle.
- Upregulation of smooth muscle M3 receptors may contribute to diverticular disease abnormalities.
Related Concept Videos
00:59Direct-Acting Cholinergic Agonists: Pharmacological Actions
Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
01:28Cholinergic Antagonists: Pharmacological Actions
Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
01:26Cholinergic Antagonists: Therapeutic Uses
Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
01:30Parasympathetic Signaling
Parasympathetic signaling plays a crucial role in regulating various physiological processes. It involves the release of acetylcholine (ACh) by parasympathetic neurons, which can have localized and short-lived effects. The majority of ACh released is rapidly inactivated at the synapse by the enzyme acetylcholinesterase (AChE), which hydrolyzes Ach into choline and acetate. Additionally, the tissue cholinesterase deactivates any ACh diffusing into the surrounding tissues.
The effects of...
The effects of...
01:27Esophageal Achalasia
Esophageal achalasia is a chronic neurogenic disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absent or ineffective peristalsis in the distal esophagus. This leads to a functional obstruction without a physical blockage, despite significant disruption of esophageal motility.EtiologyAchalasia is caused by degeneration of the myenteric (Auerbach's) plexus, specifically the loss of inhibitory ganglion cells that produce vasoactive intestinal peptide (VIP)...
01:27Diverticular Disease of the Colon
Diverticular disease involves the formation of diverticula—small sac-like outpouchings of the colonic wall—and their complications. It most commonly affects the sigmoid colon due to higher intraluminal pressure and structural vulnerability. It results from structural weakness and increased pressure in the colon, producing pseudodiverticula that may remain silent or progress to inflammation and serious complications.Structure of DiverticulaIn diverticulosis, these outpouchings are...