Nerve terminal nicotinic cholinergic receptors on excitatory motoneurons in the myenteric plexus of guinea pig intestine.
Nicotinic acetylcholine receptors (nAChRs) localized to excitatory longitudinal muscle motoneurons were studied in segments of guinea pig ileum maintained in vitro. Longitudinal muscle contractions caused by the nAChRs agonists, dimethylphenylpiperazinium (DMPP), nicotine, and cytisine were measured using isometric strain gauge transducers. In normal Krebs' solution, the nAChR agonists caused concentration-dependent biphasic contractions with a rank order potency of DMPP > cytisine = nicotine. Contractions caused by DMPP and nicotine were inhibited more than 80% by tetrodotoxin (TTX, 0.3 microM). Responses caused by DMPP were inhibited in a concentration-dependent manner by the competitive nAChR antagonist dihydro-beta-erythroidine (pA(2) = 5.4). In the presence of scopolamine (1 microM) to block muscarinic cholinergic receptors, the nAChR agonists caused longitudinal muscle contractions that were monophasic and smaller in amplitude than those recorded in the absence of scopolamine. With scopolamine present, the agonist rank order potency was nicotine = DMPP > cytisine. Contractions caused by DMPP and nicotine (each at 100 microM) were reduced by TTX by only 52 +/- 7 and 59 +/- 6%, respectively. Noncholinergic contractions caused by DMPP and nicotine were blocked by the neurokinin-1 receptor antagonist, CP 96,345-1 (0.3 microM). Dihydro-beta-erythroidine also inhibited noncholinergic contractions caused by DMPP with a pA(2) value of 5.4. It is concluded that nAChRs are localized to the somatodendritic region of excitatory longitudinal muscle motoneurons. There are also nAChRs localized to the nerve terminals of these neurons where agonists can cause noncholinergic contractions via a TTX-insensitive mechanism.
Galligan
J J
JJ
Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan, USA. galliga1@pilot.msu.edu
D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000294:innervation; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism
D018679:Cholinergic Agonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic