Sains Malaysiana 50(12)(2021):
3647-3657
http://doi.org/10.17576/jsm-2021-5012-15
Fluoxetine
Affects Intestinal Motility via 5-HT3 and Muscarinic Receptors in ex vivo Mouse Model
(Kesan Fluoxetin terhadap Motiliti Usus melalui Reseptor 5-HT3 dan Bermuskarina pada Model Tikus ex vivo)
PISSARED KHUITUAN1,2*, CHOTIKA NHAEMCHEI2,3, SAKDA PRADAB2,4, SAKENA K-DA1,2 & NIPAPORN KONTHAPAKDEE1
1Division
of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai,
Songkhla, 90110 Thailand
2Gut
Biology and Microbiota Research Unit, Prince of Songkla University, Hat Yai, Songkhla, 90110 Thailand
3Division
of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, 90110 Thailand
4Faculty
of Traditional Thai Medicine, Prince of Songkla University, Songkhla, 90110 Thailand
Diserahkan: 6 Januari 2021/Diterima: 22 Mac 2021
ABSTRACT
Fluoxetine, a
selective serotonin reuptake inhibitor anti-depressant, causes undesirable side effects, including diarrhea and
constipation. This research investigated the direct effects of fluoxetine
at 0.001, 0.01, 0.1, 1, 10, and 100 µM on duodenal and proximal colonic tissue
contractions. The investigation aimed to determine related mechanisms using an isolated mouse
intestine model. Our study showed that fluoxetine at 0.001 μM increased the
amplitude of contraction in colonic tissue but decreased the amplitude in duodenal tissue. The direct application of higher concentrations of
fluoxetine (1, 10, and 100 µM) reduced the amplitude of contractions in proximal colonic tissue. Moreover, we found that the stimulatory effect of 0.001 µM fluoxetine on the tone of contractions could
be prevented by pre-incubating the tissue in ondansetron and atropine. Our findings suggest that the inhibition of the effect
of fluoxetine was mainly mediated via 5-HT3 receptors and muscarinic signaling. These findings might
explain the conflicting gastrointestinal symptoms caused by fluoxetine.
Keywords: Intestinal contraction; selective serotonin reuptake
inhibitor; 5-hydroxytryptamine
ABSTRAK
Fluoxetin ialah perencat pengambilan anti-depresan serotonin yang memilih, menyebabkan kesan sampingan yang tidak diingini, termasuk cirit-birit dan sembelit. Penyelidikan ini mengkaji kesan langsung fluoxetin pada 0.001, 0.01, 0.1, 1, 10 dan 100 µM
pada pengecutan tisu kolon duodenum dan proksimal. Penyelidikan bertujuan untuk menentukan mekanisme yang berkaitan dengan menggunakan model usus tikus yang terpencil. Kajian menunjukkan bahawa fluoxetin pada 0.001 μM meningkatkan amplitud penguncupan pada tisu kolon tetapi menurunkan amplitud pada tisu duodenum. Aplikasi langsung kepekatan fluoxetin yang lebih tinggi (1, 10 dan 100 µM) mengurangkan amplitud pengecutanpada tisu kolon proksimal. Selain itu, didapati bahawa kesan perangsang 0.001 µM fluoxetin
pada nadapengecutan dapat dicegah dengan pra-inkubasi tisu dalam ondansetron dan atropin. Penemuan kami menunjukkan bahawa penghambatan kesan fluoxetin terutamanya dimediasi melalui reseptor 5-HT3 dan isyarat bermuskarina. Penemuan ini dapat menjelaskan gejala gastrointestinal yang bertentangan yang disebabkan oleh fluoxetin.
Kata kunci: Pengecutan usus; perencat pengambilan serotonin selektif;
5-hidroksitriptamina
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*Pengarang untuk surat-menyurat; email: pissared.k@psu.ac.th
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