S1791 R-Type Calcium Channels Mediate Inhibitory Neuromuscular Transmission and Impair Peristalsis In Vitro in the Guinea-Pig Ileum

2009 ◽  
Vol 136 (5) ◽  
pp. A-271
Author(s):  
Vinogran Naidoo ◽  
Eileen S. Rodriguez-Tapia ◽  
James Galligan
1997 ◽  
Vol 273 (5) ◽  
pp. G1127-G1134 ◽  
Author(s):  
W. MacNaughton ◽  
B. Moore ◽  
S. Vanner

This study characterized tachykinin-evoked secretomotor responses in in vitro submucosal and mucosal-submucosal preparations of the guinea pig ileum using combined intracellular and Ussing chamber recording techniques. Superfusion of endogenous tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B depolarized single submucosal neurons and evoked increased short-circuit current ( I sc) responses in Ussing chamber preparations. The NK1-receptor agonist [Sar9,Met(O2)11]SP [50% effective concentration (EC50) = 2 nM] depolarized all submucosal neurons examined. The NK3-receptor agonist senktide (EC50 = 20 nM) depolarized ∼50% of neurons examined, whereas the NK2-receptor agonist [Ala5,β-Ala8]NKA-(4—10) had no effect on membrane potential. [Sar9,Met(O2)11]SP and senktide evoked similar increases in I sc that were tetrodotoxin sensitive (91 and 100%, respectively) and were selectively blocked by the NK1antagonist CP-99,994 and the NK3antagonist SR-142801, respectively. Capsaicin-evoked increases in I sc were significantly inhibited (54%, P < 0.05) by CP-99,994 but not by SR-142801. Neither antagonist inhibited slow excitatory postsynaptic potentials. These findings suggest that tachykinin-evoked secretion in guinea pig ileum is mediated by NK1 and NK3 receptors on submucosal secretomotor neurons and that capsaicin-sensitive nerves release tachykinin(s) that activate the NK1 receptors.


1959 ◽  
Vol 197 (4) ◽  
pp. 926-928 ◽  
Author(s):  
T. Hastings Wilson ◽  
Elliott W. Strauss

Sacs of everted small intestine from a variety of animals were incubated in bicarbonate-saline containing vitamin B12 with and without intrinsic factor (IF). B12 uptake by rat intestine was stimulated only by its own intrinsic factor. Guinea pig ileum responded to all intrinsic factors tested (guinea pig, rat, hog, hamster, human being and rabbit). The intestines of hamster and rabbit were intermediate in specificity, responding to some, but not all, of the IF preparations. Species differences occur in both the intestine and intrinsic factor preparations. The guinea pig ileum was suggested as a possible assay for both hog and human IF.


2013 ◽  
Vol 7 (31) ◽  
pp. 2293-2299 ◽  
Author(s):  
Carolina de Carvalho Correia Ana ◽  
L Cibeacute rio ◽  
Macecirc do im ◽  
de Souza Monteiro Fabio ◽  
Alves de Oliveira Gislaine ◽  
...  

1984 ◽  
Vol 246 (5) ◽  
pp. G509-G514 ◽  
Author(s):  
D. H. Teitelbaum ◽  
T. M. O'Dorisio ◽  
W. E. Perkins ◽  
T. S. Gaginella

The peptides caerulein, neurotensin, somatostatin, and substance P modulate the activity of intestinal neurons and alter gut motility. We examined the effects of these peptides on acetylcholine release from the myenteric plexus and intestinal contractility in vitro. Caerulein (1 X 10(-9) M), neurotensin (1.5 X 10(-6) M), and substance P (1 X 10(-7) M) significantly enhanced the release of [3H]acetylcholine from the myenteric plexus of the guinea pig ileum. This effect was inhibited by tetrodotoxin (1.6 X 10(-6) M). Somatostatin (10(-6) M) inhibited caerulein- and neurotensin-evoked release of acetylcholine but did not inhibit release induced by substance P. Caerulein, neurotensin, and substance P caused contraction of the guinea pig ileal longitudinal muscle. Somatostatin inhibited the contractions induced by caerulein and neurotensin. In contrast, substance P-induced contraction was not inhibited significantly by somatostatin. Thus, in the guinea pig ileum, caerulein-, neurotensin-, and substance P-induced contractility is due, at least in part, to acetylcholine release from the myenteric plexus. The ability of somatostatin to inhibit peptide-induced contractility is selective, and its mechanism may be attributed to inhibition of acetylcholine release.


2000 ◽  
Vol 278 (2) ◽  
pp. G273-G280 ◽  
Author(s):  
B. A. Moore ◽  
S. Vanner

This study examined synaptic inputs from myenteric neurons innervating submucosal neurons. Intracellular recordings were obtained from submucosal S neurons in guinea pig ileal preparations in vitro, and synaptic inputs were recorded in response to electrical stimulation of exposed myenteric plexus. Most S neurons received synaptic inputs [>80% fast (f) excitatory postsynaptic potentials (EPSP), >30% slow (s) EPSPs] from the myenteric plexus. Synaptic potentials were recorded significant distances aboral (fEPSPs, 25 mm; sEPSPs, 10 mm) but not oral to the stimulating site. When preparations were studied in a double-chamber bath that chemically isolated the stimulating “myenteric chamber” from the recording side “submucosal chamber,” all fEPSPs were blocked by hexamethonium in the submucosal chamber, but not by a combination of nicotinic, purinergic, and 5-hydroxytryptamine-3 receptor antagonists in the myenteric chamber. In 15% of cells, a stimulus train elicited prolonged bursts of fEPSPs (>30 s duration) that were blocked by hexamethonium. These findings suggest that most submucosal S neurons receive synaptic inputs from predominantly anally projecting myenteric neurons. These inputs are poised to coordinate intestinal motility and secretion.


1983 ◽  
Vol 244 (4) ◽  
pp. G421-G425 ◽  
Author(s):  
H. J. Cooke ◽  
M. Montakhab ◽  
P. R. Wade ◽  
J. D. Wood

Transmural movement of 5-hydroxytryptamine (5-HT) was studied in guinea pig small intestine in vitro in order to test the hypothesis that there is mucosal 5-HT barrier in this species. Segments of guinea pig ileum were mounted as flat sheets in flux chambers or were everted and perfused. Mucosal-to-serosal (Jm leads to s) and serosal-to-mucosal (Js leads to m) fluxes of 5-HT were measured in the absence of 5-HT gradients and under open- or short-circuited conditions. The results indicated that substantial transmural movement of 5-HT occurred in these preparations. Both Jm leads to s and Js leads to m were linear functions of the 5-HT concentration over a range of 1-30 microM and were not significantly different in the two directions. Addition of 2,4-dinitrophenol to both sides of the tissue reduced short-circuit current to zero and increased both tissue conductance and unidirectional 5-HT fluxes. These results suggested that the 5-HT fluxes across the guinea pig ileum occurred by passive mechanisms. Fluxes of 5-HT across preparations with the muscularis externa removed were not significantly different from fluxes across intact preparations. Mucosal-to-serosal 5-HT fluxes in everted perfused sacs were comparable with fluxes in the flat-sheet preparations. The data are not consistent with the hypothesis of a "tissue barrier" that functions to prevent 5-HT from reaching serotonergic receptors on enteric ganglion cells or enteroendocrine cells.


2010 ◽  
Vol 65 (9-10) ◽  
pp. 627-636
Author(s):  
Fabiana de A. Cavalcante ◽  
Fabio De S. Monteiro ◽  
Italo Rossi R. Martins ◽  
Ticiano P. Barbosa ◽  
Celso de A Camara ◽  
...  

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, α-norlapachone, β-norlapachone and hydro-hydroxy- norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (CaV). As the tonic component this contraction is maintained mainly by the opening of the CaV, we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD’2 = 4.99), α-norlapachone (pD’2 = 4.49), β-norlapachone (pD’2 = 6.33), and HH-norlapachol (pD’2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As β-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 ± 0.30) · 10-5 M] suggests that the Ca2+ channel involved belongs to the type L (CaV1.2). In addition, in the functional level, the spasmolytic effect of β-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.


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.


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