Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter.
The actions of enteric 5-HT are terminated by 5-HT transporter (SERT)-mediated uptake, and gastrointestinal motility is abnormal in SERT -/- mice. We tested the hypothesis that adaptive changes in enteric 5-HT(3) receptors help SERT -/- mice survive despite inefficient 5-HT inactivation. Expression of mRNA encoding enteric 5-HT(3A) subunits was similar in SERT +/+ and -/- mice, but that of 5-HT(3B) subunits was fourfold less in SERT -/- mice. 5-HT(3B) mRNA was found, by in situ hybridization, in epithelial cells and enteric neurons. 5-HT evoked a fast inward current in myenteric neurons that was pharmacologically identified as 5-HT(3) mediated. The EC(50) of the 5-HT response was lower in SERT +/+ (18 microM) than in SERT -/- (36 microM) mice and desensitized rapidly in a greater proportion of SERT -/- neurons; however, peak amplitudes, steady-state current, and decay time constants were not different. Adaptive changes thus occur in the subunit composition of enteric 5-HT(3) receptors of SERT -/- mice that are reflected in 5-HT(3) receptor affinity and desensitization.
Liu
Min-Tsai
MT
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. ml27@columbia.edu
Rayport
Stephen
S
Jiang
Yan
Y
Murphy
Dennis L
DL
Gershon
Michael D
MD
D000200:Action Potentials; D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D003106:Colon / Q000737:chemistry / Q000294:innervation; D004247:DNA / Q000032:analysis; D004553:Electric Conductivity; D017097:Electric Impedance; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000737:chemistry / Q000294:innervation; D007422:Intestines / Q000294:innervation*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009197:Myenteric Plexus / Q000166:cytology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493231:Slc6a4 protein, mouse; D012701:Serotonin; D004247:DNA