Centrally administered adrenomedullin 5 activates oxytocin-secreting neurons in the hypothalamus and elevates plasma oxytocin level in rats

2009 ◽  
Vol 202 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Hiroki Otsubo ◽  
Susumu Hyodo ◽  
Hirofumi Hashimoto ◽  
Makoto Kawasaki ◽  
Hitoshi Suzuki ◽  
...  

We examined the effects of i.c.v. administration of adrenomedullin 5 (AM5) on the brain of conscious rats. We used porcine AM5 in the present study because rat AM5 has not been detected. We observed Fos-like immunoreactivity (LI) in the hypothalamus and brainstem of conscious rats after i.c.v. administration of AM5 (2 nmol/rat). Fos-LI, measured at 90 min post-AM5 injection, was observed in various brain areas, including the supraoptic (SON) and the paraventricular nuclei (PVN). Dual immunostaining for Fos/oxytocin (OXT) and Fos/arginine vasopressin (AVP) revealed that OXT-LI neurones predominantly colocalized Fos-LI compared with AVP-LI neurones in the SON and the PVN. Plasma OXT levels were significantly increased 5 min after i.c.v. administration of AM5 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 15 and 30 min without changes in plasma AVP levels at any time. In situ hybridization histochemistry showed that i.c.v. administration of AM5 (0.2, 1 and 2 nmol/rat) caused a marked induction of the expression of the c-fos gene in the SON and the PVN. This induction was significantly but not completely reduced by pretreatment with both the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8–37; 3 nmol/rat) and the AM receptor antagonist AM-(22–52; 27 nmol/rat). Although porcine AM5 has not been detected yet in the brain, these results suggest that centrally administered porcine AM5 may activate OXT-secreting neurosecretory cells in the hypothalamus partly through AM/CGRP receptors and elicit secretion of OXT into the systemic circulation in conscious rats.

2005 ◽  
Vol 289 (5) ◽  
pp. E753-E761 ◽  
Author(s):  
Hirofumi Hashimoto ◽  
Susumu Hyodo ◽  
Makoto Kawasaki ◽  
Takashi Mera ◽  
Lei Chen ◽  
...  

We examined the effects of intracerebroventricular (ICV) administration of adrenomedullin 2 (AM2) on plasma oxytocin (OXT) and arginine vasopressin (AVP) levels in conscious rats. Plasma OXT levels were markedly increased 5 min after ICV administration of AM2 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 10, 15, 30, and 60 min. By contrast, plasma AVP levels were not significantly elevated in samples taken between 5 and 180 min after ICV administration of AM2 except at the 30-min time point. Fos-like immunoreactivity (Fos-LI) was observed in various brain areas, including the paraventricular (PVN) and the supraoptic nuclei (SON) after ICV administration of AM2 (2 nmol/rat) in conscious rats (measured at 90 min post-AM2 infusion). Dual immunostaining for OXT/Fos and AVP/Fos showed that OXT-LI neurons predominantly exhibited nuclear Fos-LI compared with AVP-LI neurons in the PVN and the SON. In situ hybridization histochemistry showed that ICV administration of AM2 (0.2, 1, and 2 nmol/rat) caused marked induction of the expression of the c- fos gene in the PVN and the SON. This induction was significantly reduced by pretreatment with both the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8–37) (3 nmol/rat) and the AM receptor antagonist AM-(22–52) (27 nmol/rat). These results suggest that centrally administered AM2 mainly activates OXT-secreting neurons in the PVN and the SON, at least in part through the CGRP and/or AM receptors with marked elevation of plasma OXT levels in conscious rats.


1994 ◽  
Vol 266 (5) ◽  
pp. R1610-R1614
Author(s):  
K. Kato ◽  
H. Yang ◽  
Y. Tache

We investigated in conscious rats the role of capsaicin-sensitive neurons and alpha-calcitonin gene-related peptide (CGRP), the form preferentially expressed in capsaicin sensory neurons, in mediating intracisternal thyrotropin-releasing hormone (TRH) analogue-induced vagal muscarinic gastroprotection against ethanol lesions. The TRH analogue RX-77368 (1.5 ng ic) reduced by 78 and 66% gastric hemorrhagic lesions induced by intragastric intubation of 60 and 80% ethanol, respectively. alpha-CGRP (1 nmol/kg iv) inhibited by 88% gastric lesions induced by 60% ethanol, and this peptide action was blocked by the CGRP antagonist, CGRP-(8-37) (128 nmol/kg iv). The protective effect of RX-77368 against 60% ethanol was completely abolished by the CGRP monoclonal antibody 4901 (4.8 mg/kg iv), CGRP-(8-37) (128 nmol/kg iv), and capsaicin pretreatment (125 mg/kg). Gastric lesions induced by 60% ethanol were not altered by the CGRP antagonist or antibody alone but were enhanced by capsaicin pretreatment. These results suggest that the gastroprotection induced by intracisternal TRH analogue involves an interaction between central vagal efferent pathways and splanchnic sensory afferent terminals containing CGRP.


2006 ◽  
Vol 190 (2) ◽  
pp. 213-223 ◽  
Author(s):  
Makoto Kawasaki ◽  
Tatsushi Onaka ◽  
Masamitsu Nakazato ◽  
Jun Saito ◽  
Takashi Mera ◽  
...  

We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also investigated using in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8 nmol/rat). In situ hybridization histochemistry revealed that the induction of c-fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30, and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that central NPW30 may be involved in the regulation of secretion of AVP and OXT in the magnocellular neurosecretory cells in the SON and PVN.


1967 ◽  
Vol 47 (1) ◽  
pp. 165-178
Author(s):  
JOHN BRADY

1. Since 1955 Harker's work on the control of cockroach activity rhythms by a hormonal clock in the sub-oesophageal ganglion has stood largely unchallenged, but recently Roberts (1966) has questioned several of her claims; in particular he finds it impossible to transfer rhythms by implanting this ganglion. 2. Sub-oesophageal ganglia from rhythmic donors were implanted into 29 headless Periplaneta americana in a variety of ways and three different actographs used. In 2 cases the hosts showed bursts of activity for 2 or 3 days after implantation, roughly coincident with the donor's previous rhythm; a further 8 implanted animals showed rather uncertain signs of an induced rhythm, but the remaimng 19 were all apparently arrhythmic. 3. Cauterization of the neurosecretory cells of the sub-oesophageal ganglion in situ showed that cockroaches can remain rhythmic in the absence of the cells described by Harker (1960c), and probably in the absence of all cells in this ganglion which are stained by paraldehyde-fuchsin. 4. Implantation of abdominal ganglia plus their respective neurohaemal organs (Brady & Maddrell, 1967) did not elicit rhythms in eight headless hosts. 5. Cutting the circum-oesophageal commissures, or post-sub-oesophageal ganglion connectives, like beheading, appears to interfere seriously with the rhythmic expression of activity; one animal remained apparently rhythmic after this operation, however. 6. Harker's proposal for a second clock (1960b requires that phase-shifts of less than 5 hr. shall be completed within a single activity cycle; this did not occur in the twelve cases observed, phase-shifting being gradual and taking several days before reaching the entrained steady-state. 7. It is suggested that most of the divergent results of Harker, Roberts and Brady could be plausibly correlated if cockroaches have an electrical pace-maker in the brain co-ordinating rather ephemeral neuro-endocrine rhythms in the nerve-cord ganglia.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Karin Warfvinge ◽  
Diana Krause ◽  
Lars Edvinsson

Abstract Background Recent work, both clinical and experimental, suggests that the hypothalamic hormone oxytocin (OT) and its receptor (OTR) may be involved in migraine pathophysiology. In order to better understand possible central actions of OT in migraine/headache pathogenesis, we mapped the distribution of OT and OTR in nerve cells and fibers in rat brain with a focus on areas related to migraine attacks and/or shown previously to contain calcitonin gene related peptide (CGRP), another neuropeptide involved in migraine. Methods Distribution of OT and OTR in the adult, rat brain was qualitatively examined with immunohistochemistry using a series of well characterized specific antibodies. Results As expected, OT was extensively localized in the cell somas of two hypothalamic nuclei, the supraoptic (SO or SON) and paraventricular nuclei (Pa or PVN). OT also was found in many other regions of the brain where it was localized mainly in nerve fibers. In contrast, OTR staining in the brain was mainly observed in cell somas with very little expression in fibers. The most distinct OTR expression was found in the hippocampus, the pons and the substantia nigra. In some regions of the brain (e.g. the amygdala and the hypothalamus), both OT and OTR were expressed (match). Mismatch between the peptide and its receptor was primarily observed in the cerebral and cerebellar cortex (OT expression) and hippocampus (OTR expression). Conclusions We compared OT/OTR distribution in the CNS with that of CGRP and identified regions related to migraine. In particular, regions suggested as “migraine generators”, showed correspondence among the three mappings. These findings suggest central OT pathways may contribute to the role of the hypothalamus in migraine attacks.


Author(s):  
M. Sato ◽  
Y. Ogawa ◽  
M. Sasaki ◽  
T. Matsuo

A virgin female of the noctuid moth, a kind of noctuidae that eats cucumis, etc. performs calling at a fixed time of each day, depending on the length of a day. The photoreceptors that induce this calling are located around the neurosecretory cells (NSC) in the central portion of the protocerebrum. Besides, it is considered that the female’s biological clock is located also in the cerebral lobe. In order to elucidate the calling and the function of the biological clock, it is necessary to clarify the basic structure of the brain. The observation results of 12 or 30 day-old noctuid moths showed that their brains are basically composed of an outer and an inner portion-neural lamella (about 2.5 μm) of collagen fibril and perineurium cells. Furthermore, nerve cells surround the cerebral lobes, in which NSCs, mushroom bodies, and central nerve cells, etc. are observed. The NSCs are large-sized (20 to 30 μm dia.) cells, which are located in the pons intercerebralis of the head section and at the rear of the mushroom body (two each on the right and left). Furthermore, the cells were classified into two types: one having many free ribosoms 15 to 20 nm in dia. and the other having granules 150 to 350 nm in dia. (Fig. 1).


2017 ◽  
Vol 23 (1) ◽  
Author(s):  
C.A. JAWALE

Ovarian maturation by neurosecretory cells in the brain of freshwater crab, Barytelphusa cunicularis have been examined. The histological scrutiny of the brain of Barytelphusa cunicularis related with three types (A, B and C) of neurosecretory cells, which are classified on the basis of size, shape and tinctorial characters. All these types of cells marked annual cyclic changes of cytoplasmic material in association with ovarian cycle. The activity of these cells has been correlated with the ovarian cycle. They are distinguishable by their size, nature locations, shape, nucleus position, cell measure and the secretory product in the cytoplasm. The result indicates that the neurosecretory A, B and C cells of the brain seen involved in the process of mating ovulation. The neurosecretory materials staining intensity index of these cells is described.


1992 ◽  
Vol 57 (1) ◽  
pp. 194-203 ◽  
Author(s):  
Karel Šindelář ◽  
Vojtěch Kmoníček ◽  
Marta Hrubantová ◽  
Zdeněk Polívka

(Arylthio)benzoic acids IIa - IIe and VIb - VId were transformed via the acid chlorides to the N,N-dimethylamides which were reduced either with diborane "in situ" or with lithium aluminium hydride to N,N-dimethyl-(arylthio)benzylamines Ia - Ie and Vb - Vd. Leuckart reaction of the aldehydes IX and X with dimethylformamide and formic acid afforded directly the amines Va and Ve. Demethylation of the methoxy compounds Ia and Ve with hydrobromic acid resulted in the phenolic amines If and Vf. The most interesting N,N-dimethyl-4-(phenylthio)benzylamine (Va) hydrochloride showed affinity to cholinergic and 5-HT2 serotonin receptors in the rat brain and some properties considered indicative of antidepressant activity (inhibition of serotonin re-uptake in the brain and potentiation of yohimbine toxicity in mice).


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