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Cholecystokinin release mediated by 5‐HT 3 receptors in rat cerebral cortex and nucleus accumbens

Cholecystokinin release mediated by 5‐HT 3 receptors in rat cerebral cortex and nucleus accumbens 1 The effects of 5‐hydroxytryptamine (5‐HT) on the release of cholecystokinin‐like immunoreactivity (CCK‐LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mm KCl. 2 In both areas 5‐HT, tested between 0.1 and 100 nm, increased the calcium‐dependent, depolarization‐evoked CCK‐LI release in a concentration‐related manner. The concentration‐response curves did not differ significantly between the two brain areas (EC50: 0.4 + 0.045 nm and 0.48 ± 0.053 nm, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nm 5‐HT). 3 The 5‐HT1/5‐WT2 receptor antagonist methiothepin (300 nm) did not affect the CCK‐LI release elicited by 10 nm 5‐HT. However, the effects of 10 nm 5‐HT were antagonized in a concentration‐dependent manner by the 5‐HT3 receptor antagonists (3α‐tropanyl)‐1H‐indole‐3‐carboxylic acid ester (ICS 205–930; 0.1–100 nm; IC50: 3.56 ± 0.42 nm in the cortex and 3.90 ± 0.50 nm in the n. accumbens) and ondasetron (IC50: 8.15 + 0.73 nm in the cerebral cortex). 5‐HT (10 nm) was also strongly antagonized by 100 nm 1αH, 3α5αH‐tropan‐3‐yl‐3,5‐dichlorobenzoate (MDL 72222) another blocker of the 5‐HT3 receptor. Moreover, the 5‐HT3 receptor agonist 1‐phenylbiguanide (tested in the cerebral cortex between 0.1 and 100 nm) enhanced CCK‐LI release in a manner almost identical to that of 5‐HT (EC50 = 0.64 + 0.071 nm). 4 It is concluded that 5‐HT can act as a potent releaser of CCK‐LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5‐HT3 type situated on the CCK‐releasing terminals. This interaction may provide a rationale for the clinical development of both 5‐HT3 and CCK receptor antagonists as novel anxiolytic drugs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Cholecystokinin release mediated by 5‐HT 3 receptors in rat cerebral cortex and nucleus accumbens

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References (46)

Publisher
Wiley
Copyright
1991 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1991.tb09864.x
Publisher site
See Article on Publisher Site

Abstract

1 The effects of 5‐hydroxytryptamine (5‐HT) on the release of cholecystokinin‐like immunoreactivity (CCK‐LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mm KCl. 2 In both areas 5‐HT, tested between 0.1 and 100 nm, increased the calcium‐dependent, depolarization‐evoked CCK‐LI release in a concentration‐related manner. The concentration‐response curves did not differ significantly between the two brain areas (EC50: 0.4 + 0.045 nm and 0.48 ± 0.053 nm, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nm 5‐HT). 3 The 5‐HT1/5‐WT2 receptor antagonist methiothepin (300 nm) did not affect the CCK‐LI release elicited by 10 nm 5‐HT. However, the effects of 10 nm 5‐HT were antagonized in a concentration‐dependent manner by the 5‐HT3 receptor antagonists (3α‐tropanyl)‐1H‐indole‐3‐carboxylic acid ester (ICS 205–930; 0.1–100 nm; IC50: 3.56 ± 0.42 nm in the cortex and 3.90 ± 0.50 nm in the n. accumbens) and ondasetron (IC50: 8.15 + 0.73 nm in the cerebral cortex). 5‐HT (10 nm) was also strongly antagonized by 100 nm 1αH, 3α5αH‐tropan‐3‐yl‐3,5‐dichlorobenzoate (MDL 72222) another blocker of the 5‐HT3 receptor. Moreover, the 5‐HT3 receptor agonist 1‐phenylbiguanide (tested in the cerebral cortex between 0.1 and 100 nm) enhanced CCK‐LI release in a manner almost identical to that of 5‐HT (EC50 = 0.64 + 0.071 nm). 4 It is concluded that 5‐HT can act as a potent releaser of CCK‐LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5‐HT3 type situated on the CCK‐releasing terminals. This interaction may provide a rationale for the clinical development of both 5‐HT3 and CCK receptor antagonists as novel anxiolytic drugs.

Journal

British Journal of PharmacologyWiley

Published: Jul 1, 1991

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