High physiological levels of melatonin in the bile of mammals

Tan, Dun Xian; Manchester, Lucien C.; Reíter, Russel J.; Qi, Wenbo; Hanes, Martha A.; Farley, Norma J.

doi:10.1016/s0024-3205(99)00519-6

Cited by 216 publications

(183 citation statements)

References 28 publications

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“…Melatonin has special importance in the gastrointestinal tract because the enterochromaffin cells of the gut are the main source of extrapineal melatonin (Kvetnoy et al, 2002). Metabolism of melatonin in liver seems to be the major metabolic pathway for its deactivation (Lane and Moss, 1985), but active melatonin is also secreted in bile and concentrated in the gallbladder (Tan et al, 1999). Although it is well established that pineal melatonin decreases with age (Karasek, 2004), there is no information available regarding gastrointestinal melatonin.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Treatment Reverts Age-Related Changes in Guinea Pig Gallbladder Neuromuscular Transmission and Contractility

Gomez‐Pinilla¹,

Camello-Almaraz²,

Moreno³

et al. 2006

J Pharmacol Exp Ther

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The incidence of gallbladder illness increases with age, but the altered mechanisms leading to gallbladder dysfunction are poorly understood. Here we determine the age-related alterations in gallbladder contractility and the impact of melatonin treatment. Isometric tension changes in response to electrical field stimulation and to agonists were recorded from guinea pig gallbladder muscle strips. [Ca 2ϩ ] i was determined by epifluorescence microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and F-actin content was quantified by confocal microscopy. Aging reduced neurogenic contractions, which was associated with the impairment of nitrergic innervation and with increased responsiveness of capsaicin-sensitive relaxant nerves, possibly involving calcitonin gene-related peptide. Melatonin treatment for 4 weeks restored neurogenic responses to normal values, with an associated recovery of nitrergic function and the disappearance of the capsaicinsensitive component. Aging also reduced the contractile responses to cholecystokinin and Ca 2ϩ influx. The impaired contractility only correlated with diminished Ca 2ϩ mobilization in response to activation of Ca 2ϩ influx. Melatonin improved contractility and increased smooth muscle F-actin content without changing Ca 2ϩ homeostasis. In conclusion, aging impairs gallbladder function as the result of changes in the inhibitory neuromodulation of smooth muscle contractility and the reduction in the myogenic response to contractile agonists. Impaired contractility seems to be related to decreased Ca 2ϩ influx and damage of contractile proteins. Melatonin significantly ameliorated these age-related changes.

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Section: Discussionmentioning

confidence: 99%

Melatonin Treatment Reverts Age-Related Changes in Guinea Pig Gallbladder Neuromuscular Transmission and Contractility

Gomez‐Pinilla¹,

Camello-Almaraz²,

Moreno³

et al. 2006

J Pharmacol Exp Ther

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“…For instance, melatonin undergoes enterohepatic cycling; high quantities were found in the bile fluid [28]. Large amounts of this indoleamine are present in the luminal fluid, and a fraction seems to return to the tissue [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

Chronomics affirm extending scope of lead in phase of duodenal vs. pineal circadian melatonin rhythms

Pöeggeler

Cornélissen

Huether

et al. 2005

Biomedicine & Pharmacotherapy

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In Göttingen, Germany, circadian variations in melatonin had been determined time-macroscopically in pineal glands, blood plasma and duodenum of chicken and rats. When these data were metaanalyzed, they agreed with the results from an independent survey on tissues from rats collected in a laboratory in Pécs, Hungary. In the latter study, tissues were analyzed chemically in Bratislava, Slovakia, and numerically in Minneapolis, MN, USA, all by single-and multiple-component cosinor and parameter tests. In rats and chickens, these inferential statistical procedures clearly demonstrated a lead in phase of the 24-h cosine curves best fitting all of the duodenal vs. those best fitting all of the pineal melatonin values in each species in 2 geographic (geomagnetic) locations. The 24-h cosine curve of circulating melatonin was found to be in an intermediate phase position. Mechanisms of the phase differences and the contribution of gastrointestinal melatonin to circulating hormone concentrations are discussed.

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“…From there, melatonin is released into the bile, a fluid that contains in humans and other mammals several thousand pg/mL at daytime [17,18], much above the serum daytime levels that usually range between 3 and 20 pg/mL. What the function of these high levels really is, apart from the usually assumed protective role, remains to be clarified.…”

Section: -Adrenergic Receptorsmentioning

confidence: 98%

Melatonin — More than Just a Pineal Hormone

Hardeland¹

2017

BJSTR

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High physiological levels of melatonin in the bile of mammals

Cited by 216 publications

References 28 publications

Melatonin Treatment Reverts Age-Related Changes in Guinea Pig Gallbladder Neuromuscular Transmission and Contractility

Melatonin Treatment Reverts Age-Related Changes in Guinea Pig Gallbladder Neuromuscular Transmission and Contractility

Chronomics affirm extending scope of lead in phase of duodenal vs. pineal circadian melatonin rhythms

Melatonin — More than Just a Pineal Hormone

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