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 KHUITUAN^1,2*, CHOTIKA NHAEMCHEI^2,3, SAKDA PRADAB^2,4, SAKENA K-DA^1,2 & 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

Received: 6 January 2021/Accepted: 22 March 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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*Corresponding author; email: pissared.k@psu.ac.th