RT Journal Article
SR Electronic
T1 Pharmacological Properties of Nicotinic Acetylcholine Receptors Expressed by Guinea Pig Small Intestinal Myenteric Neurons
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 889
OP 897
DO 10.1124/jpet.102.033548
VO 302
IS 3
A1 Xiaoping Zhou
A1 Jim Ren
A1 Erika Brown
A1 David Schneider
A1 Yessi Caraballo-Lopez
A1 James J. Galligan
YR 2002
UL http://jpet.aspetjournals.org/content/302/3/889.abstract
AB The electrophysiological and pharmacological properties of nicotinic acetylcholine receptors (nAChRs) were studied in guinea pig small intestinal myenteric neurons maintained in culture or in acutely isolated preparations. Acetylcholine and nicotine caused inward currents that desensitized in ∼4 s. The current-voltage (I-V) relationship rectified inwardly with a reversal potential near 0 mV. The agonist rank order potency was 1,1-dimethyl-4-phenyl-piperazinium > acetylcholine = nicotine ≫ cytisine. Agonist-induced currents were blocked by nAChR antagonists with a rank order potency of mecamylamine > hexamethonium > dihydro-β-erythroidine (DHβE); mecamylamine and DHβE exhibit high potency at β4 and β2 subunit-containing nAChRs, respectively. α-Bungarotoxin (0.1 μM) or α-methyllycaconitine (0.1 μM), antagonists that block nAChRs containing α7 subunits, did not affect acetylcholine-induced responses. Immunohistochemical studies revealed that nearly every neuron in culture was labeled by an antibody (mAb35) that recognizes nAChR α3 and α5 subunits. Antibodies selective for α3, α5, or β2 subunits also stained most neurons, whereas an α7 subunit antibody revealed very few neurons. In neurons in the intact myenteric plexus from newborn and adult guinea pigs, local application of acetylcholine (1 mM) and cytisine (1 mM) caused similar amplitude depolarizations, and these responses were blocked by nAChR antagonists with a rank order potency of mecamylamine > hexamethonium > DHβE. These data indicate that myenteric neurons maintained in culture predominately express nAChRs composed of α3, α5, β2, and β4 subunits. These subunits may be in a homogenous population of receptors with unique pharmacological properties, or multiple receptors of different subunit composition may be expressed by individual neurons. The American Society for Pharmacology and Experimental Therapeutics