Publication: Kannabinoid Reseptörlerinin Sıçan Açlık İnce Bağırsak Miyoelektrik Aktivitesi Üzerine Etkisi
Abstract
Giriş-Amaç: Kannabinoid sistemin, gastrointestinal kanalda sekresyon ve mide boşalmasının yanı sıra tokluk ince ve kalın bağırsak motilitesi üzerine önemli etkileri olduğu gösterilmiştir. Ancak, kannabinoid sistemin ince bağırsak açlık miyoelektriksel aktivitesi üzerine etkisi hala bilinmemektedir. Çalışmamızın amacı, sıçanlarda periferik ve santral kannabinoid-1 reseptör (CB1R) ve kannabinoid-2 reseptörünün (CB2R) ince bağırsak açlık miyoelektriksel aktivitesinin oluşumu ve düzenlenmesindeki rollerini araştırmaktır. Yöntem: Çalışmamızda 77 adet yetişkin erkek Sprague-Dawley sıçan kullanıldı (n:7). Göç eden miyoelektrik kompleks (MMC) kaydı için sıçanların jejunumunun 3 farklı bölgesine bipolar elektrotlar yerleştirildi. Hayvanlara intraserebrovenriküler (i.s.v.) kanül veya intravenöz (i.v.) katater takıldı. İyileşme döneminin ardından 18 saatlik açlığı takiben deneyler yapıldı. Bir saatlik bazal miyoelektrik aktivitenin kaydedilmesini takiben, CB1R agonisti ACEA, hem i.v. (1,25-10 mg/kg) hem de i.s.v. (2,5-20 µg/sıçan); CB2R agonisti JWH 133, hem i.v. (1,25-10 mg/kg) hem de i.s.v. (2,5-20 µg/sıçan) yoldan verildi. CB1R antagonisti AM 251 ise, hem i.v. (0,25-2 mg/kg) hem de i.s.v. (0,25-2 µg/sıçan); CB2R antagonisti AM 630 ise, hem i.v. (0,25-2 mg/kg) hem de i.s.v. (2,5-20 µg/sıçan) yoldan uygulandı. Kombinasyon grubundaki hayvanlara ise, AM 251 (0,25 mg/kg, i.v.) uygulamasından 5 dakika sonra ACEA (5 mg/kg, i.v.) uygulandı. İstatistiksel analiz için tek yönlü varyans analizi (ANOVA) testi yapıldı ve gruplar arası çoklu karşılaştırmada Tukey-Kramer post-hoc testi kullanıldı. Bulgular: İntravenöz ACEA (2,5, 5 ve 10 mg/kg) doza bağımlı olarak spike aktivitesinde azalmaya neden olarak MMC'yi inhibe ederken (p<0,05-0,001); i.s.v. olarak uygulanan ACEA dozları etkisiz bulundu. Kombinasyon grubunda ise, i.v. ACEA'nın (5 mg/kg) inhibitör etkisi, i.v. AM 251 (0,25 mg/kg) ile tamamen baskılandı (p<0,001). Ayrıca i.v. veya i.s.v. olarak uygulanan JWH 133, AM 251 ve AM 630 MMC'de herhangi bir değişikliğe neden olmadı. Sonuçlar: Bulgularımız, eksojen olarak uygulanan ACEA'nın periferik CB1R'leri aracılığıyla açlık miyoelektrik aktivitesini inhibe ettiğini, ancak CB1R'lerin MMC'nin endojen oluşumunda rolü olmadığını düşündürmektedir. Ayrıca bulgularımız, CB2R'lerinin MMC'nin ne endojen oluşumunda ne de eksojen düzenlenmesinde rol almadığını göstermektedir. Anahtar Sözcükler: Göç Eden Miyoelektrik Kompleks, İnce Bağırsak Motilitesi, Kannabinoid-1 Reseptörler, Kannabinoid-2 Reseptörler, Sıçan
Introduction-Aim: It has been shown that the cannabinoid system has important effects on postprandial small and large intestinal motility as well as gastric emptying and secretion in the gastrointestinal tract. However, the effect of the cannabinoid system on the small intestinal myoelectrical activity in fasted state is still unknown. The aim of our study was to investigate the roles of peripheral and central cannabinoid-1 receptor (CB1R) and cannabinoid-2 receptor (CB2R) in the formation and regulation of small intestine fasting myoelectrical activity in rats. Methods: In our study, 77 adult male Sprague-Dawley rats were used (n:7). Bipolar electrodes were placed in 3 different regions of the jejunum of rats for migrating myoelectric complex (MMC) recording. Intracerebroventricular (i.c.v) cannula or intravenous (i.v) catheter were placed to the animals. Following the recovery period, experiments were performed after an 18-hour fasting period. Following one-hour recording of baseline myoelectric activity, while CB1R selective agonist, ACEA, was administered i.v (1.25-10 mg/kg) or i.c.v (2.5-20 µg/rat); CB2R agonist, JWH 133 was administered i.v (1.25-10 mg/kg) or i.c.v (2.5-20 µg/rat). Additionally, when CB1R antagonist, AM 251, was injected i.v (0.25-2 mg/kg) or i.c.v (0.25-2 µg/rat); CB2R antagonist, AM 630 was injected i.v (0.25-2 mg/kg) or i.c.v (2.5-20 µg/rat). In the combination group animals were received ACEA (5 mg/kg, i.v) 5 minutes after AM 251 (0.25 mg/kg, i.v) administration. One-way analysis of variance (ANOVA) test was performed for statistical analysis and Tukey-Kramer post-hoc test was used for multiple comparisons between groups. Results: While intravenous ACEA (2.5, 5 and 10 mg/kg) inhibited MMC by causing a dose-dependent decrease in spike activity (p<0.05-0.001), i.c.v ACEA doses were ineffective. Additinonally, the inhibitory effect of i.v ACEA (5 mg/kg) was completely abolished by i.v AM 251 (0.25 mg/kg) (p<0.001). Furthermore, JWH 133, AM 251 and AM 630 administered i.v or i.c.v did not cause any change in MMC. Conclusions: Our findings suggest that exogenously administered ACEA inhibits fasting myoelectric activity by peripheral CB1Rs, but CB1Rs have no role in the endogenous formation of MMC. Additionally, our findings propose that CB2Rs are involved in neither endogenous formation nor exogenous regulation of MMC. Keywords: Migrating Myoelectric Complex, Small Intestine Motility, Cannabinoid-1 Receptor, Cannabinoid-2 Receptor, Rat
Introduction-Aim: It has been shown that the cannabinoid system has important effects on postprandial small and large intestinal motility as well as gastric emptying and secretion in the gastrointestinal tract. However, the effect of the cannabinoid system on the small intestinal myoelectrical activity in fasted state is still unknown. The aim of our study was to investigate the roles of peripheral and central cannabinoid-1 receptor (CB1R) and cannabinoid-2 receptor (CB2R) in the formation and regulation of small intestine fasting myoelectrical activity in rats. Methods: In our study, 77 adult male Sprague-Dawley rats were used (n:7). Bipolar electrodes were placed in 3 different regions of the jejunum of rats for migrating myoelectric complex (MMC) recording. Intracerebroventricular (i.c.v) cannula or intravenous (i.v) catheter were placed to the animals. Following the recovery period, experiments were performed after an 18-hour fasting period. Following one-hour recording of baseline myoelectric activity, while CB1R selective agonist, ACEA, was administered i.v (1.25-10 mg/kg) or i.c.v (2.5-20 µg/rat); CB2R agonist, JWH 133 was administered i.v (1.25-10 mg/kg) or i.c.v (2.5-20 µg/rat). Additionally, when CB1R antagonist, AM 251, was injected i.v (0.25-2 mg/kg) or i.c.v (0.25-2 µg/rat); CB2R antagonist, AM 630 was injected i.v (0.25-2 mg/kg) or i.c.v (2.5-20 µg/rat). In the combination group animals were received ACEA (5 mg/kg, i.v) 5 minutes after AM 251 (0.25 mg/kg, i.v) administration. One-way analysis of variance (ANOVA) test was performed for statistical analysis and Tukey-Kramer post-hoc test was used for multiple comparisons between groups. Results: While intravenous ACEA (2.5, 5 and 10 mg/kg) inhibited MMC by causing a dose-dependent decrease in spike activity (p<0.05-0.001), i.c.v ACEA doses were ineffective. Additinonally, the inhibitory effect of i.v ACEA (5 mg/kg) was completely abolished by i.v AM 251 (0.25 mg/kg) (p<0.001). Furthermore, JWH 133, AM 251 and AM 630 administered i.v or i.c.v did not cause any change in MMC. Conclusions: Our findings suggest that exogenously administered ACEA inhibits fasting myoelectric activity by peripheral CB1Rs, but CB1Rs have no role in the endogenous formation of MMC. Additionally, our findings propose that CB2Rs are involved in neither endogenous formation nor exogenous regulation of MMC. Keywords: Migrating Myoelectric Complex, Small Intestine Motility, Cannabinoid-1 Receptor, Cannabinoid-2 Receptor, Rat
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