Calcium-calmodulin-dependent Activation of Adenylate Cyclase in Prostaglandin-induced Electrically-monitored Intestinal Secretion in the Rat

Hardcastle, J; Hardcastle, P T; Ayton, B.; Chapman, JC; MacNeil, Sheila

doi:10.1111/j.2042-7158.1992.tb03568.x

Cited by 11 publications

(1 citation statement)

References 26 publications

(17 reference statements)

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“…The effects of PDE4 inhibition on cAMP that results in decreased smooth muscle contractility [12] , together with cAMP-associated increases in bowel secretion [23,24] can explain most of the present results on fecal pellet output, fecal wet weight and fecal water content. In addition to the direct smooth muscle relaxation effects of PDE4 inhibitors [12] , PDE4 inhibition can also reduce electric field stimulation-induced contraction of the intestine.…”

Section: Discussionmentioning

confidence: 65%

Inhibition of Phosphodiesterase Type 4 Decreases Stress-Induced Defecation in Rats and Mice

et al. 2007

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Background/Aims: Phosphodiesterase type 4 (PDE4) has been previously shown to regulate colonic contractile activity in vitro. In this study, the effects of PDE4 inhibition were assessed in a model of stress-induced defecation previously demonstrated to be due to increased colonic transit/evacuation. Methods: Rats were individually placed in a mild restraint cage and placed into a 12°C environment (cold-restraint stress) for 60 min. Mice received restraint (only) stress at room temperature for 30 min. Loperamide (positive control compound) or two different PDE4 inhibitors (rolipram and roflumilast) were administered orally at several doses to the rodents 1 h before stress began. Vehicle alone was administered for comparison. The number of fecal pellets expelled during stress (fecal pellet output), total fecal pellet wet weight and total fecal water content were measured. Results: Loperamide produced a dose-related decrease (ID₅₀s in mg/kg) in fecal pellet output (rat = 7.4, mouse = 0.7) and significantly decreased fecal wet weight (72.9%) and decreased fecal percent water content (9.4%). The two PDE4 inhibitors produced a similar dose-related inhibition of fecal pellet output. Rolipram exhibited ID₅₀s in rat and mouse of 14.1 and 27.1, respectively. Rolipram significantly decreased fecal wet weight (58.8%) but increased fecal percent water content (15.0%). For roflumilast, ID₅₀s were 24.2 mg/kg and 12.4 in the rat and mouse, respectively. Although roflumilast also significantly (p < 0.05) decreased fecal wet weight (47.2%), it did not significantly increase fecal percent water content. Conclusions: These data indicate that PDE4 inhibition is effective in reducing rodent stress-induced defecation, provides the first functional data on a potential role for PDE4 activity in the colonic evacuation response to stress, and indicates the potential utility of PDE4 inhibitors in functional bowel disease such as irritable bowel syndrome requires further evaluation.

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Section: Discussionmentioning

confidence: 65%

Inhibition of Phosphodiesterase Type 4 Decreases Stress-Induced Defecation in Rats and Mice

et al. 2007

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Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways

Petersen

Goergen

Höfken

et al. 1993

Naunyn-Schmiedeberg's Arch Pharmacol

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In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO3- secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO3- transport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO3- and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO3- flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and L-propranolol; the Cl- channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)ocytl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO3(-)-free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to cAMP synthesis sufficient to turn part of electroneutral HCO3- secretion electrogenic. In a search for the involved signalling pathways, the H1-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimic the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 x 10(-7) mol/l) completely transformed HCO3- secretion into an electrogenic process. The VIP receptor antagonist (4Cl-DPhe6, Leu17) VIP, delayed and reduced the Isc responses to Ba2+ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba2+ is likely to act by releasing VIP from neural terminals.

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Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides

Basson

1996

Cancer Letters

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Calcium-calmodulin-dependent Activation of Adenylate Cyclase in Prostaglandin-induced Electrically-monitored Intestinal Secretion in the Rat

Cited by 11 publications

References 26 publications

Inhibition of Phosphodiesterase Type 4 Decreases Stress-Induced Defecation in Rats and Mice

Inhibition of Phosphodiesterase Type 4 Decreases Stress-Induced Defecation in Rats and Mice

Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways

Regulation of human Caco-2 intestinal epithelial brush border enzyme activity by cyclic nucleotides

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