Structure‐specific effects of lipidated oxytocin analogs on intracellular calcium levels, parental behavior, and oxytocin concentrations in the plasma and cerebrospinal fluid in mice

نویسندگان

  • Stanislav M. Cherepanov
  • Shigeru Yokoyama
  • Akira Mizuno
  • Wataru Ichinose
  • Olga Lopatina
  • Anna A. Shabalova
  • Alla B. Salmina
  • Yasuhiko Yamamoto
  • Hiroshi Okamoto
  • Satoshi Shuto
  • Haruhiro Higashida
چکیده

Oxytocin (OT) is a neuroendocrine nonapeptide that plays an important role in social memory and behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects in some clinical trials. As a central nervous system (CNS) drug, however, OT has two unfavorable characteristics: OT is short-acting and shows poor permeability across the blood-brain barrier, because it exists in charged form in the plasma and has short half-life. To overcome these drawbacks, an analog with long-lasting effects is required. We previously synthesized the analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues. In this study, we synthesized and evaluated the analogs lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which feature the conjugation of one palmitoyl group at the cysteine and tyrosine residues, respectively. In human embryonic kidney-293 cells overexpressing human OT receptors, these three LOTs demonstrated comparably weak effects on the elevation of intracellular free calcium concentrations after OT receptor activation, compared to the effects of OT. The three LOTs and OT exhibited different time-dependent effects on recovery from impaired pup retrieval behavior in sires of CD38-knockout mice. Sires treated with LOT-1 showed the strongest effect, whereas others had no or little effects at 24 h after injection. These results indicated that LOTs have structure-specific agonistic effects, and suggest that lipidation of OT might have therapeutic benefits for social impairment.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques.

There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-rangi...

متن کامل

Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans

There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 I...

متن کامل

Inhibitory effects of oxytocin on the inflammatory parameters and vascular endothelial growth factor (VEGF) in the rat air pouch model of inflammation

Introduction: The aim of the present study was to evaluate the effect of oxytocin on the angiogenesis and inflammatory parameters in air pouch model of inflammation. Methods: Inflammation was induced by injection of carrageenan into pouches in male Wistar rats. Oxytocin (4.25, 8.5 and 17 μg) was administered intra pouch at the same time as the carrageenan and then for 2 consecutive days. Af...

متن کامل

کاهش کراتین کیناز- MB به‌دنبال تجویز اکسی‌توسین در دوره‌های ایسکمی- رپرفیوژن قلب ایزوله موش صحرایی

Background: Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide (NO), prostacyclin and mitoc...

متن کامل

Oxytocin improves autistic-like behaviors induced by maternal deprivation in female rats

Background and Objective: Maternal deprivation as an early life negative experience can lead to enduring disorders such as autism-like behaviors by affecting brain development. Oxytocinergic system alters in the process of maternal deprivation, on the other hand the positive effect of oxytocin on the improvement of social behavior and stereotyped behavior in autism disorder has been shown. In t...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2017