Developmental differences in the expression of the cholera toxin sensitive subunit (Gs alpha) of adenylate cyclase in the rat small intestine.

We examined the role of 5-hydroxytryptamine (5-HT) in cholera toxin (CT)-induced mucin secretion in the proximal and distal regions of the rat small intestine. Neither the 5-HT2 receptor antagonist ketanserin nor the cyclooxygenase inhibitor indomethacin was capable of inhibiting choleraic mucin secretion. However, in the presence of the mixed 5-HT3/4 receptor antagonist tropisetron at doses that block both receptor subtypes, the secretory response was reduced to baseline levels in the proximal and distal small intestine. The selective 5-HT3 receptor antagonist ondansetron had no significant effect. These findings suggest that choleraic mucin secretion is mediated primarily through the activation of a 5-HT4-like receptor. Mucin secretion in response to the exogenous application of 5-HT occurs via two pathways: one is mediated by a 5-HT4-like receptor and is capsaicin sensitive but tetrodotoxin (TTX) insensitive, and one lacks the capsaicin-sensitive 5-HT4-mediated response but is TTX sensitive. Both converge on a common pathway that is cholinergic. No significant differences were observed between proximal and distal intestinal segments.

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Adenylate cyclase from rabbit small intestine: Activation by cholera toxin and interaction with calcium

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(85)90728-3 ◽

1985 ◽

Vol 239 (2) ◽

pp. 587-594 ◽

Cited By ~ 4

Author(s):

Pedro S. Lazo ◽

Francisco Barros ◽

Pedro Domínguez ◽

Alfonso Rivaya ◽

Gloria Velasco

Keyword(s):

Small Intestine ◽

Adenylate Cyclase ◽

Cholera Toxin ◽

Rabbit Small Intestine

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The effect of iloprost on the ADP-ribosylation of Gsα (the α-subunit of Gs)

Biochemical Journal ◽

10.1042/bj2610841 ◽

1989 ◽

Vol 261 (3) ◽

pp. 841-845 ◽

Cited By ~ 29

Author(s):

L Molina y Vedia ◽

R D Nolan ◽

E G Lapetina

Keyword(s):

Adenylate Cyclase ◽

Cholera Toxin ◽

Alpha Subunit ◽

Α Subunit ◽

Present Evidence ◽

Adp Ribosylation ◽

Specific Antisera ◽

Membrane Bound ◽

Gs Alpha ◽

Adp Ribosyltransferase

Treatment of platelets with a prostacyclin analogue, iloprost, decreased the cholera-toxin-induced ADP-ribosylation of membrane-bound Gs alpha (alpha-subunit of G-protein that stimulates adenylate cyclase; 42 kDa protein) and a cytosolic substrate (44 kDa protein) [Molina y Vedia, Reep & Lapetina (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5899-5902]. This decrease is apparently not correlated with a significant change in the quantity of membrane Gs alpha, as detected by two Gs alpha-specific antisera. This finding contrasts with the suggestion in a previous report [Edwards, MacDermot & Wilkins (1987) Br. J. Pharmacol. 90, 501-510], indicating that iloprost caused a loss of Gs alpha from the membrane. Our evidence points to a modification in the ability of the 42 kDa protein to be ADP-ribosylated by cholera toxin. This modification of Gs alpha might be related to its ADP-ribosylation by endogenous ADP-ribosyltransferase activity. Here we present evidence showing that Gs alpha was ADP-ribosylated in platelets that had been electropermeabilized and incubated with [alpha-32P]NAD+. This endogenous ADP-ribosylation of Gs alpha is inhibited by nicotinamide and stimulated by iloprost.

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Pituitary adenylate cyclase activating polypeptides, PACAP-27 and PACAP-38: stimulators of electrogenic ion secretion in the rat small intestine

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1992.tb14363.x ◽

1992 ◽

Vol 106 (2) ◽

pp. 498-502 ◽

Cited By ~ 29

Author(s):

Helen M. Cox

Keyword(s):

Small Intestine ◽

Adenylate Cyclase ◽

Rat Small Intestine ◽

Ion Secretion ◽

Pituitary Adenylate Cyclase

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Neural mediation of cholera toxin-induced mucin secretion in the rat small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.265.6.g1050 ◽

1993 ◽

Vol 265 (6) ◽

pp. G1050-G1056 ◽

Cited By ~ 6

Author(s):

B. A. Moore ◽

K. A. Sharkey ◽

M. Mantle

Keyword(s):

Small Intestine ◽

Cholera Toxin ◽

Fold Increase ◽

Open Loop ◽

Sensory Nerves ◽

Loop Model ◽

Rat Small Intestine ◽

Mucin Secretion ◽

Distal Small Intestine

We examined the role of enteric nerves in cholera toxin (CT)-induced mucin secretion in proximal and distal regions of rat small intestine. Stimulation of intestinal loops with 120 micrograms (1.5 mumol) CT using an in vitro open-loop model resulted in an approximately four-fold increase in luminal mucin content over unstimulated controls in both regions of the gut. Prior treatment of loops with tetrodotoxin had no effect on the amount of mucin released in response to CT. However, permanent destruction of primary sensory afferent nerves by neonatal treatment of rats with capsaicin reduced the mucin response to CT to baseline levels in both regions. In normal animals, atropine resulted in approximately 40% inhibition of mucin secretion in both the proximal and distal small intestine. The atropine-sensitive secretory response appears to be a component of the capsaicin-sensitive response. These results suggest that choleraic mucin secretion is mediated primarily by a capsaicin-sensitive neurogenic pathway involving local activation of sensory nerves, which may then elicit mucin secretion through interaction with cholinergic nerves.

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