title: Regional differences in neostigmine-induced contraction and relaxation of stomach from diabetic guinea pig.
abstract: Delayed gastric emptying and autonomic neuropathy have been documented in patients with diabetes mellitus. Some medications used to treat delayed gastric emptying enhance release of acetylcholine from autonomic neurons to strengthen gastric contractions. Autonomic coordination among gastric regions may be altered in diabetes resulting in poor outcomes in response to prokinetic drugs. Fundus, antrum, and pylorus from STZ or control guinea pigs were treated with neostigmine to mimic release of acetylcholine from autonomic neurons by prokinetic agents. In diabetic animals, neostigmine-induced contractions were weaker in fundus and pylorus but similar in antrum. The muscarinic receptor antagonist 4-DAMP or the nicotinic receptor antagonist hexamethonium reduced neostigmine-induced contractions. Activation of presynaptic muscarinic receptors on nitrergic neurons was impaired in fundus and antrum from diabetic animals. Nerve-stimulated contractions and relaxations, number of nNOS myenteric neurons, and tissue choline content were reduced in fundus from diabetic animals. Despite reduced number of myenteric neurons, tissue choline content was increased in antrum from diabetic animals. Since cholinergic motility of each gastric region was affected differently by diabetes, prokinetic drugs that nondiscriminately enhance acetylcholine release from autonomic neurons may not effectively normalize delayed gastric emptying in patients with diabetes and more selective medications may be warranted.
authors.affiliation: Department of Physiology, Chicago College of Osteopathic Medicine, Midwestern University, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cellini
authors.forename: Karyn
authors.initials: K
authors.lastname: DiNovo
authors.forename: Jessica
authors.initials: J
authors.lastname: Harlow
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: LePard
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D010277:Parasympathomimetics; D009388:Neostigmine