흰쥐 턱밑샘에서 fluoxetine 투여에 의한 침분비 및 muscarinic acetylcholine receptor M3 발현 감소
Reduction of salivation and muscarinic acetylcholine receptor M3 expression in the submandibular gland of the rat by chronic fluoxetine administration
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침분비저하, 구강건조증 및 침 성분의 변화를 포함한 비정상적인 침분비는 항우울제복용과 관련된 중요한 부작용이다. 선택적 세로토닌 재흡수 억제제(SSRI) 항우울제 또한 이러한 부작용을 가지고 있다. 하지만 SSRI에 의한 침분비저하 기전과 항콜린성 작용은 완전히 밝혀지지 않았다. 본 연구에서는 fluoxetine 의 만성 투여 후 쥐의 침샘에서 침분비와 콜린성 신호 단백질 수치의 변화를 확인하였다. 동물은 정상군, 저농도경구투여군(20 mg/kg p.o.), 고농도경구투여군(40 mg/kg p.o.), 저농도복강투여군(20 mg/kg i.p.) 그리고 고농도복강투여군(40 mg/kg i.p.)으로 구분하였다. 4주 동안 fluoxetine 투여 후, 침을 수집하여 침분비량을 측정하였다. 후에 침샘 조직을 적출하여 muscrinic acetylcholine receptor M3 (mAchR M3) 와aquaporin5 (AQP5) 항체를 이용하여 단백질 정량을 하였다. 그 결과 복강투여군에서 침 분비량의 감소가나타났지만, 경구투여군에서는 나타나지 않았다. 이 감소 패턴은 mAchR M3 와 AQP5 단백질 수치에서도유사하게 나타났다. 이러한 결과는 fluoxetine에 의한 침분비저하가 항콜린성 작용과 관련이 있음을 시사한다.
Abstract
Abnormal salivation including hyposalivation, xerostomia, and changes in saliva composition is important side effect related to taking antidepressants. Selective serotonin re-uptake inhibitor (SSRI) antidepressants have also these side effects. However, hyposalivation mechanism and anticholinergic action by SSRIs is not fully understood. In this study, we have examined changes in salivation and cholinergic signal proteins levels in the salivary gland of the rat after chronic fluoxetine administration. Animals were divided in to 5 groups with the control, lowdose p.o. (20 mg/kg p.o.), highdose p.o. (40 mg/kg p.o.), lowdose i.p. (20 mg/kg i.p.) and highdose i.p. (40 mg/kg i.p.) groups. After fluoxetine administration for 4 weeks, saliva collection began to determine the salivary flow rate. Next, salivary glands were removed, the salivary tissues processes for Western blot analysis (for muscrinci acetylcholine receptor M3 (mAchR M3) and aquaporin5 (AQP5)). The salivary flow rate was decreased with fluoxetine dose in the i.p. groups, but not in the p.o. groups. This decreasing pattern was similar to mAchR M3 and AQP5 protein level. These finding suggest that the hyposalivation by fluoxetine may related anticholinergic action.
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