Faculty of Health Sciences & Medicine

Future Research Projects

STIMULATION OF MUSCARINIC RECEPTOR SUBTYPES AND ITS EFFECTS ON SMOOTH MUSCLE TONE AND NITRIC OXIDE RELEASE IN THE INTERNAL ANAL SPHINCTER

Supervisor

Professor Russ Chess-Williams
Professor of Human Physiology

BACKGROUND

Faecal incontinence affects >11% of the general population (2 million Australian adults) and although not life threatening it has a large impact on the quality of life for patients and is a huge economic burden on the Australian health system.   In adults aged >60y the prevalence is even higher (almost 20%) which equates to 379,000 sufferers of faecal incontinence in this age group.  The treatments for faecal incontinence all have varying rates of success and most are associated with unwanted side effects. The internal anal sphincter (IAS) is responsible for maintaining up to 85% of resting anal tone and therefore a better understand of this smooth muscle’s function could lead to the development of better treatments for faecal incontinence that are more specific and have fewer side effects.

The internal anal sphincter (IAS) is innervated by the parasympathetic nervous system but this tissue responds in a complex fashion to the neurotransmitter acetylcholine (Ach): direct contraction via stimulation of smooth muscle muscarinic receptors and an indirect relaxation via the release of nitric oxide.  There are 5 subtypes of muscarinic receptor and which subtypes are found in the IAS are unknown.

The IAS also has an inner epithelial layer which releases factors that can regulate tone of the smooth muscle.  Epithelial cells in other tissues such as the bladder can release nitric oxide in response to stretch and muscarinic receptor stimulation but whether this occurs in the IAS is unknown.

AIMS OF THE PROJECT

  1. To identify which muscarinic receptor subtypes are present in the IAS.
  2. To identify which of these receptors mediates contraction of this tissue.
  3. To investigate the effects of muscarinic receptor stimulation on nitric oxide release from the muscle and epithelial layers of the IAS.

METHODS

  • Radioligand binding studies with [3H]QNB to address aim (1)
  • Isolated tissue bath studies to address aim (2)
  • Nitric oxide selective electrode to address aim (3)