Investigation of the 5-hydroxytryptamine receptor mediating the ?transient? short-circuit current response in guinea-pig ileal mucosa

1995 ◽  
Vol 351 (6) ◽  
Author(s):  
E. Leung ◽  
D. Blissard ◽  
M.F. Jett ◽  
R.M. Eglen
Keyword(s):  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Current Response ◽  
Ileal Mucosa

Effects of neurotransmitter release on mucosal transport in guinea pig ileum

1983 ◽  
Vol 245 (6) ◽  
pp. G745-G750 ◽  
Author(s):  
H. J. Cooke ◽  
K. Shonnard ◽  
G. Highison ◽  
J. D. Wood
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Neurotransmitter Release ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Scorpion Venom ◽  
Enteric Neurons ◽  
Sodium Absorption ◽  
Guinea Pig Ileum ◽  
Ileal Mucosa

Scorpion venom (Leiurus quinquestriatus), a substance that evokes neurotransmitter release by depolarizing neurons, was used to activate enteric neurons in short-circuited guinea pig ileum. Scorpion venom increased transmural potential difference and short-circuit current, and this response was similar to the increase that occurred after electrical stimulation of enteric neurons. The stimulus- or venom-evoked response in short-circuit current was abolished by tetrodotoxin. Atropine reduced by 47% the increments in short-circuit current produced by either electrical stimulation or venom. Scorpion venom increased active chloride secretion in short-circuited guinea pig ileal mucosa but had no significant effect on active sodium absorption, residual flux, or total tissue conductance. No morphological changes in transmission electron micrographs of ileal mucosa treated with scorpion venom were evident compared with controls. Alanine caused an increase in short-circuit current in venom-treated tissue that was similar to control values. These results show that scorpion venom mimics the mucosal effects of electrical activation of enteric neurons. These results suggest that a significant component of both scorpion venom action and the response to electrical field stimulation is mediated by neural release of acetylcholine, which activates epithelial muscarinic receptors.

Suppression of gastric acid secretion by furosemide in isolated gastric mucosa of guinea pig

1980 ◽  
Vol 239 (6) ◽  
pp. G532-G535 ◽  
Author(s):  
A. Ayalon ◽  
A. Corcia ◽  
G. Klemperer ◽  
S. R. Caplan
Keyword(s):  
Guinea Pig ◽  
Acid Secretion ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Electrical Conductance ◽  
Short Circuit Current ◽  
Cl Transport ◽  
Consequent Reduction ◽  
Net Flux ◽  
Mucosal Side

The effect of furosemide on acid secretion and Cl- transport was studied in isolated fundic mucosa of the guinea pig. Furosemide (10(-3) M), applied to the serosal side produced an immediate effect on the short-circuit current (Isc), lowering it by 47 +/- 2%. Potential difference decreased by 29 +/- 3%, electrical conductance by 18 +/- 4%, acid secretion by 38 +/- 1%, and net flux of Cl- from serosal-to-mucosal side by 37%. Application of the drug to the mucosal side produced similar effects on acid secretion and on the electrical parameters. It is suggested that furosemide blocks the entrance of Cl-, by the Na+--Cl- cotransport mechanism, through the basolateral membrane of the secreting cell. The consequent reduction in electrogenic Cl- transport would cause Isc and acid secretion to decrease. A reduction of Cl- conductance of the apical membrane, upon mucosal application of the drug, would cause similar effects on acid secretion and Cl- transport.

Cellular pathways mediating tachykinin-evoked secretomotor responses in guinea pig ileum

1997 ◽  
Vol 273 (5) ◽  
pp. G1127-G1134 ◽  
Author(s):  
W. MacNaughton ◽  
B. Moore ◽  
S. Vanner
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Short Circuit Current ◽  
Neurokinin A ◽  
Guinea Pig Ileum ◽  
Cellular Pathways ◽  
20 Nm

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.

Alterations in capsaicin-evoked electrolyte transport during the evolution of guinea pig TNBS ileitis

2002 ◽  
Vol 282 (6) ◽  
pp. G972-G980 ◽  
Author(s):  
Paula Miceli ◽  
Gerald P. Morris ◽  
Wallace K. MacNaughton ◽  
Stephen Vanner
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrolyte Transport ◽  
Secretory Function ◽  
Trinitrobenzenesulfonic Acid ◽  
Ussing Chambers ◽  
Circulating Cytokines

The efferent secretomotor activity of capsaicin-sensitive nerves was monitored during the evolution of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis in the guinea pig by recording changes in short-circuit current (Δ I sc) in response to capsaicin, substance P (SP), and carbachol. Submucosal-mucosal preparations mounted in standard Ussing chambers were studied at time 0, at 8 h, and 1, 3, 5, 7, 14, and 30 days following the intraluminal instillation of TNBS or saline. Maximal Δ I scresponses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated Δ I sc were also significantly reduced. Similar attenuation in capsaicin and carbachol responses was observed in jejunal tissue 20 cm proximal to the inflamed site at day 7. These studies demonstrate that efferent secretomotor function of capsaicin-sensitive nerves is maintained early in TNBS ileitis but significantly reduced by 24 h. By day 7, defects in enterocyte secretory function at inflamed and noninflamed sites also occurred, an effect that may be mediated by circulating cytokines.

5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in guinea pig distal colon

1998 ◽  
Vol 275 (4) ◽  
pp. G829-G834 ◽  
Author(s):  
Atsukazu Kuwahara ◽  
Hirofumi Kuramoto ◽  
Makoto Kadowaki
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Evoked Response ◽  
Evoked Responses ◽  
No Donor ◽  
Simultaneous Application

The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)-evoked chloride secretion in guinea pig distal colon was examined. Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase in short-circuit current ( I sc) was used as an index of secretion. Addition of 5-HT to the serosal side produced a concentration-dependent (10−7–10−5M) increase in I sc caused by chloride secretion. N G-nitro-l-arginine (l-NNA) significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to 61.1 and 70.6% of control, respectively. Neurally evoked response was also inhibited by l-NNA. The NO donor sodium nitroprusside (SNP, 10−4 M) increased basal I sc mainly because of chloride secretion. The SNP-evoked response was significantly reduced by tetrodotoxin but was unchanged by atropine or indomethacin. These results suggest that the 5-HT-evoked increase in I sc is associated with an NO-generating mechanism. Atropine significantly reduced the 5-HT (10−5 M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control, respectively. Simultaneous application of atropine andl-NNA further decreased the 5-HT-evoked responses more than either drug alone; application ofl-NNA and atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of atropine-treated tissues, respectively. These results suggest that noncholinergic components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively, and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of the noncholinergic component of the 5-HT-evoked responses. The results provide evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked chloride secretion in guinea pig distal colon.

Transmural fluxes of 5-hydroxytryptamine in guinea pig ileum

1983 ◽  
Vol 244 (4) ◽  
pp. G421-G425 ◽  
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.

Intestinal mucosal cyclic GMP: regulation and relation to ion transport

1976 ◽  
Vol 231 (1) ◽  
pp. 275-282 ◽  
Author(s):  
TA Brasitus ◽  
M Field ◽  
DV Kimberg
Keyword(s):  
Causal Relationship ◽  
Cyclic Gmp ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ileal Mucosa ◽  
Muscarinic Cholinergic Receptors ◽  
Cholecystokinin Octapeptide ◽  
Muscarinic Cholinergic ◽  
Stimulation Of

Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven.

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