Enhanced nerve-stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea-pigs.
Summary of "Enhanced nerve-stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea-pigs."
1 Diabetes mellitus can lead to neuropathy of enteric neurons, resulting in abnormal gut motility. These studies investigated voltage-dependent contributions of muscarinic M(3) receptor activation by acetylcholine and neurokinin NK(1) receptor activation by neurokinins to nerve-stimulated contractions of longitudinal ileal strips from STZ guinea-pigs, a type 1 diabetic model with insulin deficiency, but mild hyperglycaemia. 2 Contractions to bethanechol, substance P methyl ester, and nerve stimulation were greater in diabetic as compared to control ileum. 3 The muscarinic M(3) receptor antagonist 4-DAMP at lower voltages and the neurokinin NK(1) receptor antagonist SR140333 at higher voltages, but not the neurokinin NK(1) receptor antagonist CP-96,345, were more effective at inhibiting nerve-stimulated immediate peak contractions and total areas of contraction of ileum from diabetic as compared to control animals. For diabetic ileum, voltage-dependent increases in the areas of nerve-stimulated contraction were observed in the presence of 4-DAMP and CP-96,345 but not SR140333. 4 At low voltages only, nerve-stimulated release of acetylcholine was greater from diabetic as compared to control ileum. 5 Fluorescence intensity of tachykinin-like immunoreactivity was increased in ileal myenteric ganglia from diabetic as compared to control animals. 6 In diabetic guinea-pigs, stronger ileal nerve-stimulated contractions reflected increased release of acetylcholine at lower voltages and tachykinins at higher voltages, as well as increased sensitivity of smooth muscle M(3) and NK(1) receptors to acetylcholine and tachykinins. Hypoinsulinaemia may be a primary contributor to intestinal motility dysfunction in type 1 diabetes mellitus.
Affiliation
Department of Physiology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
Journal Details
This article was published in the following journal.
Name: Autonomic & autacoid pharmacology
ISSN: 1474-8673
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22676206
- DOI: http://dx.doi.org/10.1111/j.1474-8673.2012.00471.x
Medical and Biotech [MESH] Definitions
Receptors, Neurokinin-3
A class of cell surface receptors for tachykinins that prefers neurokinin B (neurokinin beta, neuromedin K) over other tachykinins. Neurokinin-3 (NK-3) receptors have been cloned and are members of the G-protein coupled receptor superfamily. They have been found in the central nervous system and in peripheral tissues.
Receptors, Neurokinin-2
A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.
Receptors, Tachykinin
Cell surface proteins that bind tachykinins with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, substance P, neurokinin A (substance K, neurokinin alpha, neuromedin L), and neurokinin B (neurokinin beta, neuromedin K).
Muscarinic Agonists
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
Receptor, Muscarinic M4
A specific subtype of muscarinic receptor found in the CORPUS STRIATUM and the LUNG. It has similar receptor binding specificities to MUSCARINIC RECEPTOR M1 and MUSCARINIC RECEPTOR M2.
PubMed Articles
The cholinergic response is increased in isolated ileum from gastroschisis rat model.
INTRODUCTION: Babies with gastroschisis (G) have high morbidity rate and long hospital stay due to bowel hypomotility caused by chronic exposure of the bowel to the amniotic fluid. Our aim was to eval...
To determine if the muscarinic agonist, bethanechol, inhibits the non-cholinergic, atropine-resistant (i.e. putatively purinergic) component of naturally occurring (i.e. reflexogenic) bladder contract...
Role of tachykinin and neurokinin receptors in the regulation of ovine omasal contractions.
The present study investigated a role of tachykinins (TK) and neurokinin (NK) receptors (NK-R) in the non-cholinergic regulation of omasal contractions in sheep. Semiquantitative reverse transcription...
Effects of a muscarinic receptor agonist oxotremorine-M (oxo-M) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced...
ABSTRACT: BACKGROUND: To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions. METHODS: The urethra and bladder of 9 male guine...
Clinical Trials
Nerve blocks are an effective way to control pain after surgery. There are two major nerves that provide sensation to the knee: the femoral nerve provides sensation to the front of the kne...
Sleeve Gastrectomy With Ileal Switch for Diabetes Control
Ileal interposition shifts a segment of ileum proximally to achieve maximal meal stimulated GLP-1 secretion and coupled with a restrictive procedure of sleeve gastrectomy helps in achievin...
THVD-201 is a novel combination of a muscarinic antagonist (tolterodine) and a muscarinic agonist (pilocarpine).
Pilot Study of Electronic Uterine Contraction Inhibitor
The objective is to test a novel paradigm for the inhibition of human preterm uterine contractions. The study hypothesis is that human preterm contractions can be safely inhibited with a...
Nerve Stimulation to Modify a Spinal Reflex
This study will determine whether stimulating the nerves or the brain can modify the spinal reflex that controls the muscles that flex and extend the ankle. Training spinal nerve networks...
