GPR39 receptor expression in the mouse brain

Jackson, Valerie R.; Nothacker, Hans‐Peter; Civelli, Olivier

doi:10.1097/01.wnr.0000215779.76602.93

Cited by 102 publications

(71 citation statements)

References 15 publications

(25 reference statements)

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“…However, using in situ hybridization and RT-PCR, subsequent studies did not find expression of this receptor in the hypothalamus [21,22,32]. More importantly, recent studies and the retraction of initial findings by Zhang clearly established that obestatin is not the endogenous ligand that binds to GRP39 receptor [9,21,22,32,52]. In the present study, we found that ip injection of obestatin has no effect on the Fos expression pattern in the hypothalamus and brainstem.…”

Section: Discussioncontrasting

confidence: 48%

“…This was supported by the fact that obestatin was originally claimed to bind the GPR-39, which is highly expressed in the hypothalamus, as detected by Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) [51]. However, using in situ hybridization and RT-PCR, subsequent studies did not find expression of this receptor in the hypothalamus [21,22,32]. More importantly, recent studies and the retraction of initial findings by Zhang clearly established that obestatin is not the endogenous ligand that binds to GRP39 receptor [9,21,22,32,52].…”

Section: Discussionmentioning

confidence: 99%

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Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

et al. 2008

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Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 μmol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n = 8/group) or ad libitum (n = 10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 μmol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n = 4/group). Additionally, fasted mice were injected ip with obestatin (1 μmol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

et al. 2008

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“…Mice treated with morphine showed significant higher pain sensitivity 90 and 120 min after morphine injection compared to first measurement (60 min) of the same group [F (3,28) (Fig. 4).…”

Section: The Effect Of Obestatin On Analgesic Effect Induced By Acutementioning

confidence: 94%

“…It was also characterized as an activator of the orphan G protein-coupled GPR39 receptor and was found to be the main ligand for it. The highest levels of GPR39 mRNA were detected by in-situ hybridization in the amygdala, the hippocampus, and the auditory cortex, while lower levels were found in several other brain regions but surprisingly no expression of GPR39 was found in the hypothalamus in mice [3]. GPR39 receptor has two splice variants, GPR39-1a and GPR39-1b.…”

Section: Introductionmentioning

confidence: 98%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5 μg/2 μl) was administrated once a day in all experiments. Furthermore, 0.2 mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20 mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120 min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.

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“…4,5 Another study found GPR39 expression in the rodent amygdala, hippocampus, auditory cortex and other brain regions but not the hypothalamus. 6 Since the original study, however, two other groups have failed to activate the GPR39 receptor with obestatin. 7,8 Initial studies showed that obestatin has opposing effects to ghrelin.…”

Section: Introductionmentioning

confidence: 99%

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

et al. 2007

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Objective: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. Context: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. Study design: Case-control study. Setting: Hospital-based study. Patients: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. Intervention: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). Main outcome measure: The response of obestatin to a meal in the different groups. Results: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.874 vs 17.272 pg/ml, P ¼ 0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.874 vs 21.973 pg/ml, P ¼ 0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.0470.003 vs 0.0570.009, P ¼ 0.32), but this was higher in the gastrectomy group (0.0470.003 vs 0.170.01, Po0.001). Conclusions: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

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GPR39 receptor expression in the mouse brain

Cited by 102 publications

References 15 publications

Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

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