Identification of cells that express 5- hydroxytryptamine1A receptors in the nervous systems of the bowel and pancreas

Abstract

Although serotonin (5-HT)1A receptors are known to be present on neural elements in both the bowel and the pancreas, the precise location of these receptors has not previously been determined. Earlier investigations have suggested that 5-HT1A receptors are synthesized in enteric, but not pancreatic ganglia, and that they mediate pre-and postjunctional inhibition. Wholemount in situ hybridization was used to identify cells that contain mRNA encoding 5-HT1A receptors, and immunocytochemistry was employed to locate receptor protein. mRNA encoding 5-HT1A receptors was found in the majority of neurons in both submucosal and myenteric plexuses. 5-HT1A immunoreactivity, however, was abundant only on the surfaces of a limited subset of nerve cell bodies and processes. 5-HT-immunoreactive axons were found in close proximity to sites of 5-HT1A immunoreactivity. Myenteric, but not submucosal calbindin-immunoreactive neurons (with Dogiel type II morphology) were surrounded by rings of 5-HT1A immunoreactivity. The cytoplasm of the cell bodies and dendrites of a small subset of Dogiel type I neurons was also intensely 5-HT1A immunoreactive. Most of the Dogiel type I 5-HT1A-immunoreactive myenteric neurons, and some of the type II neurons that were ringed by 5-HT1A immunoreactivity became doubly labeled following injections of the retrograde tracer, FluoroGold (FG), into the submucosal plexus. 5-HT1A-immunoreactive neurons in distant submucosal ganglia also became labeled by retrograde transport of FG. None of the 5-HT1A-immunoreactive cells were labeled by the intraluminal administration of the beta-subunit of cholera toxin, a marker for vasoactive intestinal peptide-containing secretomotor neurons. These observations suggest that some of the myenteric 5-HT1A-immunoreactive neurons project to submucosal ganglia and that the submucosal 5-HT1A-immunoreactive cells are interneurons. In addition to neurons, a subset of 5-HT-containing enterochromaffin cells expressed 5-HT1A immunoreactivity, which was co-localized with 5-HT in secretory granules. In the pancreas, 5-HT1A immunoreactivity was observed in ganglia, acinar nerves, and glucagonimmunoreactive islet cells. Serotonergic enteropancreatic axons have been found to terminate in close proximity to each of these structures, which may thus be the targets of this innervation. The abundance of 5-HT1A receptor immunoreactivity on nerves of the gut and pancreas suggests that drugs designed to interact with these receptors may have unanticipated visceral actions.

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

“…To date, the only data identifying a possible transmitter mediating the myenteric IPSPs comes from a limited study, which found that the 5-HT 1A receptor antagonist NAN-190 blocked IPSPs in some AH/Dogiel type II neurons [54]. Many AH/Dogiel type II neurons express 5-HT 1A receptors [64] and are hyperpolarized by 5-HT acting on these receptors [39,42]. Electrical stimulation of descending pathways including the axons of neurons containing 5-HT evokes slow EPSPs in many AH/Dogiel type II neurons [83] and blockade of 5-HT 7 receptors can convert the slow EPSPs into slow hyperpolarizations.…”

Mechanical stimulation activates Gαq signaling pathways and 5-hydroxytryptamine release from human carcinoid BON cells

“…Mechanical stimulation generated by direct contact of the enterochromaffin cells with the luminal contents occurs frequently throughout the intestinal tract. Others have reported that balloon distention, puffs of nitrogen gas ejected from a pipette, and stroking with a brush evoke 5-HT release (31,32). Many of these stimuli are composed of several different forces acting simultaneously.…”

Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans

“…glucagon-like peptide 1 [GLP-1] analogues used for treating type 2 diabetes) is a successful example of this approach [4,5]. Serotonin (5-hydroxytryptamine ) receptors are expressed in rodent islets [6][7][8] and virtually all 5-HT receptors (5-HT 1-7 ) are G protein-coupled with the exception of 5-HT 3 receptors (ligand-gated K + and Na + ion channels) [9]. Recently, microarray and RNA sequencing analyses revealed transcripts of almost all 5-HT receptors in human islets [10,11].…”