5-HTP works in the brain and central nervous system by increasing the production of the chemical serotonin. Serotonin can affect sleep, appetite, temperature, sexual behavior, and pain sensation. Since 5-HTP increases the synthesis of serotonin, it is used for several diseases where serotonin is believed to play an important role including depression, insomnia, obesity, and many other conditions.
Osteoclast differentiation was assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity. After 5 days of culture, cells were stained for TRAP kit using a leukocyte acid phosphatase kit (Sigma Aldrich, St Louis, MO, USA). Cells with three or more nuclei were counted as multinucleated mature osteoclasts. To measure TRAP activity, cells were fixed with 10% formalin for 10 min and 95% ethanol for 1 min, and then 100 μl of citrate buffer (50 mM, pH 4.6) containing 10 mM sodium tartrate and 5 mM p-nitrophenylphosphate (Sigma-Aldrich) was added to the wells containing fixed cells in the 48-well plates. After incubation for 1 h, enzyme reaction mixtures in the wells were transferred to new plates containing an equal volume of 0.1 N NaOH. Absorbance was measured at 410 nm using a microplate reader.
Thymosin beta(4), a small ubiquitous protein containing 43 aa, has structure/function activity via its actin-binding domain and numerous biological affects on cells. Since it is the major actin-sequestering molecule in eukaryotic cells and is found essentially in all cells and body fluids, thymosin beta(4) has the potential for significant roles in tissue development, maintenance, repair, and pathology. Several active sites with unique functions have been identified, including the amino-terminal site containing 4 aa (Ac-SDKP) that generally blocks inflammation and reduces fibrosis. Another active site at the amino terminus contains 15 aa, including Ac-SDKP, and promotes cell survival and blocks apoptosis, while a short sequence containing LKKTETQ, the central actin-binding domain (aa 17-23) plus 1 additional amino acid (Q), promotes angiogenesis, wound healing, and cell migration. Several additional biological activities have been identified but not yet localized in the molecule, including its antimicrobial activity, the induction of various genes (including laminin-5, MMPs, TGF beta, zyxin, terminal deoxynucleotidyl transferase, and angiogenesis-related proteins), and the ability to activate ILK/PINCH/Akt, and other signaling molecules important in both apoptosis and inflammatory pathways. This review details these important physiologically and pathologically active sites and their potential therapeutic uses.
Virtually all vertebrates have an oxytocin-like nonapeptide hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually located close to each other (less than 15,000 bases apart) on the same chromosome, and are transcribed in opposite directions (however, in fugu, the homologs are further apart and transcribed in the same direction).
Nature has been very clever in a way. Without oxytocin, you know, babies are what they really are - I probably shouldn't say this on TV - but noisy, smelly animals that don't actually do anything useful. And, um, that's what oxytocin does. It gives them a special salience, a special beauty and allows us to bond with these defenceless little animals.
The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist Sir Henry Hallett Dale in 1906, and its milk ejection property was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911. In the 1920s, oxytocin and vasopressin were isolated from pituitary tissue and given their current names. The word oxytocin was coined from the term oxytocic, Greek ὀξύς, oxys, and τοκετός , toketos, meaning "quick birth".
In 19 obese females given either placebo or 8mg/kg (weight not actually given, only BMI between 30-40 for women) daily for 5 weeks without any concurrent dietary recommendations, 5-HTP treatment was associated with a decrease in appetite and food intake (resulting in weight loss) without significantly affecting mood state. This study noted that food intake was reduced from an average of 2,903kcal to 1,819kcal (62% of baseline) while placebo only reduced calories to 80%, and the 0.5kg weight loss in placebo was outperformed by a near 1.5kg loss in 5-HTP. These weight loss effects have been noted with 750mg 5-HTP over 2 weeks in overweight diabetics and over 12 weeks in obese persons given 900mg 5-HTP daily (58% of baseline intake); this latter study had a 6 week trial without a diet (in which significant weight loss was only noted at week 6) followed up by coadministration with a diet where weight loss proceeded to reach an additional 3.3kg over the subsequent 6 weeks; this latter study is duplicated in Medline.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone and dynorphin, for example, that act locally. The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.
Three groups of mice were individually placed in cages with aggressive mice and experienced social defeat, a stressful experience for them. One group was missing its oxytocin receptors, essentially the plug by which the hormone accesses brain cells. The lack of receptors means oxytocin couldn't enter the mice's brain cells. The second group had an increased number of receptors so their brain cells were flooded with the hormone. The third control group had a normal number of receptors.
In regards to interventions, one study in treatment resistant depressed persons that combination therapy of 5-HTP with Carbidopa noted that 43 out of 99 (43.4%) patients improved with an average 200mg (variable 50-600mg) dosage of 5-HTP. It has been noted that since Cardidopa is a peripheral decarboxylase inhibitor that can prevent metabolism of monoamines including serotonin that these results are unlikely to reflect monotherapy with 5-HTP, despite being within the 30-45% range sometimes seen with the placebo effect.
Myocardial infarction and heart failure are severe causes for death in humans. Extracellular nucleotides (ATP and ADP) released at the site of myocardial damage induce thrombosis, apoptosis and necrosis. ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1, CD39) rapidly hydrolyzes ATP and ADP to AMP. An in vivo myocardial ischemia/reperfusion injury test in transgenic mice expressing human CD39 resulted in a decrease of the infarct size. The same transgene including the human CD39 cDNA driven by the murine MHC class I gene H-2Kb promoter was used for the generation of transgenic pigs via SCNT. Expression of human CD39 was detected on circulating blood cells and in myocardial tissue of the transgenic animals. After in vivo induction of myocardial ischemia/reperfusion injury, a reduction of the myocardial injury analogous to the results in the transgenic mice was found (Wheeler et al., 2012).
Oral 5-HTP results in an increase in urinary 5-HIAA, a serotonin metabolite, indicating that 5-HTP is peripherally metabolized to serotonin, which is then metabolized. This might cause a false positive test in tests looking for carcinoid syndrome. Due to the conversion of 5-HTP into serotonin by the liver, there could be a risk of heart valve disease from serotonin's effect on the heart, as based on preclinical findings. However, 5-HTP has not been associated with cardiac toxicity in humans.