Sa1741 Vpac1 Receptors Localised to Cholinergic Secretomotor Neurons Regulate Intestinal Secretion in Guinea-Pig Jejunum

2013 ◽  
Vol 144 (5) ◽  
pp. S-296
Author(s):  
Candice Fung ◽  
Jaime Pei Pei Foong ◽  
Laura J. Parry ◽  
Joel C. Bornstein
2014 ◽  
Vol 306 (9) ◽  
pp. G748-G758 ◽  
Author(s):  
Candice Fung ◽  
Petra Unterweger ◽  
Laura J. Parry ◽  
Joel C. Bornstein ◽  
Jaime P. P. Foong

In the gastrointestinal tract, vasoactive intestinal peptide (VIP) is found exclusively within neurons. VIP regulates intestinal motility via neurally mediated and direct actions on smooth muscle and secretion by a direct mucosal action, and via actions on submucosal neurons. VIP acts via VPAC1 and VPAC2 receptors; however, the subtype involved in its neural actions is unclear. The neural roles of VIP and VPAC1 receptors (VPAC1R) were investigated in intestinal motility and secretion in guinea pig jejunum. Expression of VIP receptors across the jejunal layers was examined using RT-PCR. Submucosal and myenteric neurons expressing VIP receptor subtype VPAC1 and/or various neurochemical markers were identified immunohistochemically. Isotonic muscle contraction was measured in longitudinal muscle-myenteric plexus preparations. Electrogenic secretion across mucosa-submucosa preparations was measured in Ussing chambers by monitoring short-circuit current. Calretinin+ excitatory longitudinal muscle motor neurons expressed VPAC1R. Most cholinergic submucosal neurons, notably NPY+ secretomotor neurons, expressed VPAC1R. VIP (100 nM) induced longitudinal muscle contraction that was inhibited by TTX (1 μM), PG97–269 (VPAC1 antagonist; 1 μM), and hyoscine (10 μM), but not by hexamethonium (200 μM). VIP (50 nM)-evoked secretion was depressed by hyoscine or PG97–269 and involved a small TTX-sensitive component. PG97–269 and TTX combined did not further depress the VIP response observed in the presence of PG97–269 alone. We conclude that VIP stimulates ACh-mediated longitudinal muscle contraction via VPAC1R on cholinergic motor neurons. VIP induces Cl− secretion directly via epithelial VPAC1R and indirectly via VPAC1R on cholinergic secretomotor neurons. No evidence was obtained for involvement of other neural VIP receptors.


2007 ◽  
Vol 292 (2) ◽  
pp. G608-G614 ◽  
Author(s):  
David E. Reed ◽  
Stephen Vanner

This study examined whether mucosal stimulation activates long secretomotor neural reflexes and, if so, how they are organized. The submucosa of in vitro full thickness guinea pig ileal preparations was exposed in the distal portion and intracellular recordings were obtained from electrophysiologically identified secretomotor neurons. Axons in the intact mucosa of the oral segment were stimulated by a large bipolar stimulating electrode. In control preparations, a single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in 86% of neurons located 0.7–1.0 cm anal to the stimulus site. A stimulus train evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether mucosal stimulation specifically activated mucosal sensory nerve terminals, the mucosa/submucosa was severed from the underlying layers and repositioned. In these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion with phorbol dibutyrate enhanced excitability of sensory neurons and pressure-pulse application of serotonin to the mucosa increased the fast EPSPs evoked by mucosal stimulation, providing further evidence that sensory neurons were involved. To determine whether these reflexes projected through the myenteric plexus, this plexus was surgically lesioned between the stimulus site and the impaled neuron. No fast EPSPs were recorded in these preparations following mucosal stimulation whereas lesioning the submucosal plexus had no effect. These results demonstrate that mucosal stimulation triggers a long myenteric pathway that activates submucosal secretomotor neurons. This pathway projects in parallel with motor and vasodilator reflexes, and this common pathway may enable coordination of intestinal secretion, blood flow, and motility.


2009 ◽  
Vol 136 (1) ◽  
pp. 299-308.e4 ◽  
Author(s):  
Rachel M. Gwynne ◽  
Melina Ellis ◽  
Henrik Sjövall ◽  
Joel C. Bornstein

1986 ◽  
Vol 64 (7) ◽  
pp. 993-998 ◽  
Author(s):  
Beverley Greenwood ◽  
Stephanie Diamant ◽  
J. S. Davison

The aim of the experiments was to examine, in vitro, the role of the enteric nervous system in the relationship between motor activity and transmural potential difference (PD) in the guinea pig jejunum and colon using the nerve blocking agents tetrodotoxin (TTX) and aconitine. Histological data showed that perfusion of the intestinal segments with gassed Hepes solution was essential for the maintenance of transmural PD. Disruption of the mucosa was associated with a loss of spontaneous fluctuations in transmural PD without any loss of spontaneous motor activity. Under spontaneous conditions, a neural pathway exists linking jejunal and colonic motility with transmural PD. However, in some cases a mechanical link was also apparent, as an attenuated TTX and aconitine–resistant component.


1995 ◽  
Vol 269 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
S. Vanner ◽  
W. K. MacNaughton

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.


1974 ◽  
Vol 63 (2) ◽  
pp. 311-317 ◽  
Author(s):  
J. R. MAINOYA ◽  
H. A. BERN ◽  
J. W. REGAN

SUMMARY Mucosal fluid, sodium and chloride transfer were measured in everted sacs of rat, guinea-pig and hamster jejunum, and in rat ileum and colon, and in guinea-pig gall bladder. After treatment of the animal with ovine prolactin, a highly significant enhancement of fluid and NaCl absorption was observed in rat, hamster and guinea-pig jejunum. Prolactin treatment caused a significant increase in fluid and NaCl transfer in rat ileum, but not in guinea-pig ileum or rat colon. Prolactin administration had no consistent effect on fluid and NaCl absorption by the guinea-pig gall bladder. The several regions of the mammalian gut appear to differ in their responsiveness to prolactin.


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