Cortistatin Inhibits Intestinal Secretion in the Guinea‐pig Ileum In Vitro

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.

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Some species differences in the intrinsic factor stimulation of B12 uptake by small intestine in vitro

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1959.197.4.926 ◽

1959 ◽

Vol 197 (4) ◽

pp. 926-928 ◽

Cited By ~ 21

Author(s):

T. Hastings Wilson ◽

Elliott W. Strauss

Keyword(s):

Small Intestine ◽

Guinea Pig ◽

Species Differences ◽

Intrinsic Factor ◽

Vitamin B ◽

Guinea Pig Ileum ◽

Rat Intestine ◽

Intrinsic Factors ◽

Stimulation Of

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.

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Somatostatin modulation of peptide-induced acetylcholine release in guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.246.5.g509 ◽

1984 ◽

Vol 246 (5) ◽

pp. G509-G514 ◽

Cited By ~ 5

Author(s):

D. H. Teitelbaum ◽

T. M. O'Dorisio ◽

W. E. Perkins ◽

T. S. Gaginella

Keyword(s):

Substance P ◽

Guinea Pig ◽

Myenteric Plexus ◽

Acetylcholine Release ◽

Longitudinal Muscle ◽

Guinea Pig Ileum ◽

Gut Motility ◽

Release Of Acetylcholine

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.

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Properties of synaptic inputs from myenteric neurons innervating submucosal S neurons in guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.278.2.g273 ◽

2000 ◽

Vol 278 (2) ◽

pp. G273-G280 ◽

Cited By ~ 16

Author(s):

B. A. Moore ◽

S. Vanner

Keyword(s):

Guinea Pig ◽

Myenteric Plexus ◽

Intracellular Recordings ◽

Guinea Pig Ileum ◽

Myenteric Neurons ◽

Synaptic Inputs ◽

Stimulus Train ◽

Stimulation Of ◽

Double Chamber

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.

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Transmural fluxes of 5-hydroxytryptamine in guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1983.244.4.g421 ◽

1983 ◽

Vol 244 (4) ◽

pp. G421-G425 ◽

Cited By ~ 5

Author(s):

H. J. Cooke ◽

M. Montakhab ◽

P. R. Wade ◽

J. D. Wood

Keyword(s):

Guinea Pig ◽

Ganglion Cells ◽

Short Circuit ◽

Short Circuit Current ◽

Linear Functions ◽

Guinea Pig Ileum ◽

Serotonergic Receptors ◽

Flat Sheet ◽

Muscularis Externa

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.

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Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.2.g203 ◽

1995 ◽

Vol 269 (2) ◽

pp. G203-G209 ◽

Cited By ~ 10

Author(s):

S. Vanner ◽

W. K. MacNaughton

Keyword(s):

Guinea Pig ◽

Ion Transport ◽

Short Circuit ◽

Ussing Chamber ◽

Sensory Nerve ◽

Nerve Fibers ◽

Sensory Nerves ◽

Guinea Pig Ileum ◽

Secretomotor Neurons

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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