摘要:

AbstractThere is now wide acceptance that ATP and other nucleotides are ubiquitous extracellular chemical messengers. ATP and diadenosine polyphosphates can be released from synaptosomes. They act on a large and diverse family of P2 purinoceptors, four of which have been cloned. This receptor family can be divided into two distinct classes: ligand‐gated ion channels for P2X receptors and G protein‐coupled receptors for P2Y, P2U, P2T and P2D receptors. The P2Y, P2U and P2D receptors have a fairly wide tissue distribution, while the P2X receptor is mainly found in neurons and muscles and the P2T and P2Z receptors confined to platelets and immune cells, respectively. lnositol phosphate and calcium signalling appear to be the predominant mechanisms for transducing the G‐protein linked P2 receptor signals. Multiple P2 receptors are expressed by neurons and glia in the CNS and also in neuroendocrine cells. ATP and other nucleotides may therefore have important roles not only as a neurotransmitter but also as a neuroendocrine regulatory mess

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00671.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractNeonatally handled (H) animals, as adults, exhibit lower ACTH and corticosterone (B) responses to a number of acute stressors compared to their non‐handled (NH) counterparts. However, little is known about activity within the hypothalamic‐pituitary‐adrenal (HPA) axis of H and NH animals under conditions of chronic stress. We, therefore, examined HPA function in adult H and NH rats exposed to chronic intermittent cold stress (4 h of 4°C cold a day for 21 days; H CHR and NH CHR) and in control H and NH (H CTL and NH CTL) rats. H CTL and NH CTL animals displayed comparable ACTH and B responses to a single, acute exposure to cold. We found that H CHR animals exhibited lower levels of ACTH, but not B, during the 21st exposure to cold (the homotypic stressor) compared to the first exposure to cold in H CTL; however, ACTH and B levels in NH CHR were not different from those in NH CTL. In contrast, NH CHR animals hypersecreted ACTH and B in response to restraint (the novel, heterotypic stressor) compared to NH CTL and both H groups, whereas H CHR and H CTL animals did not differ in their responses to restraint. These endocrine responses were associated with increased basal median eminence levels of both CRH and AVP in H CHR and NH CHR relative to their control groups (with NH CHR exhibiting the highest absolute levels of each secretagogue), and with decreased glucocorticoid receptor densities in septum of both H CHR and NH CHR. In addition, the expected lower glucocorticoid receptor density in hippocampus and frontal cortex of NH rats compared to H rats was observed. We believe that the difference in glucocorticoid receptor density between H and NH animals in the hippocampus and frontal cortex aid the associated differences in secretagogue content in the median eminence are related to the hypersecretion of ACTH and B in the NH CHR relative to the other groups. Furthermore, we hypothesize that an active inhibitory process is involved in the adaptation of HPA responses of H CHR animals to the homotypic stressor, and present a working model of regulation of activity within the CRH/AVP neurons in t

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00672.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractCentral administration of neurotensin (NT) stimulates hypothalamic‐pituitary‐adrenal (HPA) activity in freely‐moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 rnin following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1–8and NT8–13only NT8–13was found to significantly elevate ACTH and B levels. Moreover, NT8–13activated the HPA axis with a temporal profile similar to NT1–13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor.Animals pre‐treated intravenously with the corticotropin‐releasing hormone (CRH) antagonist, α‐helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT‐induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stirnulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT el

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00673.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractReceptive behavior in females vertebrates is controlled by hormones, principally estrogen, secreted by the ovary. Estrogen influences behavior by interacting with a specific estrogen binding protein, or receptor, located in target cells in certain hypothalamic nuclei. To better understand the molecular mechanisms involved in the control of receptive behavior in whiptail lizards, we investigated the effects of exogenous estrogen on t h e regulation of estrogen receptor and progesterone receptor expression in several regions of the brains of Cnernidophorus uniparens. First we determined a dosage of 17β‐estradiol 3‐benzoate (0.5 μg) which reliably induced receptive behavior in ovariectomized C. uniparens. Then using in situ hybridization, we examined the effects of that dosage on the expression of estrogen receptor and progesterone receptor mRNA in the brain 24 h after injection. Estrogen treatment resulted in a significant up‐regulation of estrogen receptor mRNA expression in the ventromedial nucleus of the hypothalamus and torus semicircularis, down‐regulation of estrogen receptor mRNA expression in the lateral septum, and no change in the periventricular nuclei of the hypothalamus, the periventricular nucleus of the preoptic area, and the dorsal hypothalamus. The same dosage resulted in increased progesterone receptor mRNA expression in the ventromedial nucleus of the hypothalamus and the periventricular nucleus of the preoptic area; no significant changes in progesterone receptor mRNA expression were observed in the periventricular nuclei of the hypothalamus or the torus semicircularis, although the differences in progesterone receptor expression in the torus semicircularis approached statistical significance. The up‐regulation of estrogen receptor gene expression by estrogen in the ventromedial nucleus of the hypothalamus of lizards is opposite to that reported in female rats in which estrogen down‐regulates estrogen receptor expression in the ventromedial nucleus of the hypothalamus. We propose that this may be related to differences in reproductive physiology between vertebrates which have extended follicular phases and prolonged periods of estrus and rats, which have an abbreviated follicular phase and brief peri

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00674.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe effects of the thyroid hormones on target cells are mediated through nuclear T3receptors. In the peripheral nervous system, nuclear T3receptors were previously detected with the monoclonal antibody 283 rnAb in all the primary sensory neurons throughout neuronal life and in peripheral glia at the perinatal period only (Eur. J. Neurosci. 5, 379, 7993). To determine whether these nuclear T3receptors correspond to functional ones able to bind T3, cryostat sections and in vitro cell cultures of dorsal root ganglion (DRG) or sciatic nerve were incubated with 0.1 nM [1251]‐labeled T3, either alone to visualize the total T3‐binding sites or added with a lo3 fold excess of unlabeled T3to estimate the part due to the non‐specific T3‐binding. After glutaraldehyde fixation, radioautography showed that the specific T3‐binding sites were largely prevalent. The T3‐binding capacity of peripheral glia in DRG and sciatic nerve was restricted to the perinatal period in vivo and to Schwann cells cultured in vitro. In all the primary sensory neurons, specific T3‐binding sites were disclosed in foetal as well as adult rats. The detection of the T3‐binding sites in the nucleus indicated that the nuclear T3receptors are functional. Moreover the concomitant presence of both T3‐binding sites and T3receptors CI isoforms in the perikaryon of DRG neurons infers that: 1) [1251]‐labeied T3can be retained on the T3‐binding ‘E’ domain of nascent CI, isoform molecules newly‐synthesized on the perikaryal ribosomes; 2) the CI isoforms translocated to the nucleus are modified by posttranslational changes and finally recognized by 2B3 rnAb as nuclear T3receptor. In conclusion, the radioautographic visualization of the T3‐binding sites in peripheral neurons and glia confirms that the nuclear T3receptors are functional and contributes to clarify t h e discordant intracellular localization provided by the immunocytochemical detection of nuclear T3recepto

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00675.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractSixty min supine restraint stress induced a marked, but transient, hypothermic response in intact male rats, which tended to recover towards pre‐stress levels or slightly overshoot during the later stages of restraint. Castration reduced the initial hypothermia but increased overshoots. Baseline (pre‐stress) core temperature was also higher in castrated than intact rats, but the reduction in stress‐induced hypothermia was still present even when this difference had been taken into account. The hypothermic response was not altered during the course of 10 sessions of daily repeated restraint in either intact or castrated rats. Castration did not alter cardiac responses to restraint. Both intact and castrated rats showed marked tachycardia during the initial 12 min of restraint, followed by a gradual fall towards baseline values. Repeated restraint accentuated the second phase of the cardiac response, without modifying the initial tachycardia, in both intact and castrated animals. The response of blood corticosterone levels to the first period of restraint was unaltered by castration but the attenuation observed after 10 sessions of stress was more complete in castrated rats.The neuronal c‐fos response 60 min after the last of the series of repeated restraints was less in the hypothalamic paraventricular nucleus, medial amygdala, and locus coeruleus compared with that following the first session, but not in the lateral septum or the bed nucleus of the stria terminalis. Castration did not change the c‐fos profile following the same number of restraint sessions. Castration depleted completely the vasopressinergic innervation in the lateral septum, diagonal band of Broca and medial amygdala.Five mg/kg naloxone i.p. prior to the onset of stress resulted in persistent hypothermic responses throughout the stress period in intact males. This was reduced in castrated rats. Blockade of prostaglandins synthesis by 12 mg/kg indornethacin i.p. 3 h prior to stress had little effect on hypothermic stress responses.The results of these experiments suggest that an androgen‐dependent process, possibly AVP‐containing systems in the forebrain, may regulate both baseline and stress‐induced levels of core temperature and have selective effects on components of the response to stress, including restraint‐induced hypothermia and the adaptation of corticoid responses to repeated restraint. Steroid‐dependent opioid systems may also be implicated in the hypotherrnic response

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00676.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe hypothalamic suprachiasmatic nuclei (SCN) constitute both the biological clock of many circadian rhythms, and the first relay in the transmission of light cues from the retina to the pineal gland, which releases, via nocturnal melatonin secretion, an endocrine expression of the daylength. The aim of the present work was to investigate the precise role of the SCN in the entrainment of the nocturnal rhythm of melatonin (MEL) in sheep. Bilateral lesions of the SCN were performed via a transsinusal surgical approach in 10 adult rams submitted to a constant photoperiod (16L:8D). Lesioned rams were compared to 4 sham and 2 control animals. Blood samples were collected 8 days before, 8 days after, and one month after surgery. Plasma MEL levels were estimated using direct radioimmunoassay. At the end of the experiment, histology and immunohistochemistry of the suprachiasmatic area were performed, and the extent of lesions was evaluated using a computerized image analysis system. Six rams exhibited a complete lesion of the SCN, and in the four remaining animals, the lesions were restricted to the anterior part of the SCN. For all animals, the nocturnal melatonin secretion was altered, but depending on the extent of the lesion, two types of results were observed:Eight days after surgery, in 3 of the 4 rams bearing anterior lesions of the SCN (SCNJ, a nocturnal increase in melatonin secretion still occurred at dusk, but the duration of this secretion extended beyond the end of the night. One month after surgery, melatonin profiles were once again normal, as compared to sham animals. The fourth SCN, ram exhibited a cyclic MEL secretion not synchronized with the light cycle 8 days after surgery, and synchronized with dusk but not dawn one month after surgery.Eight days after surgery, all the rams bearing complete lesions of the SCN (SCNZ) showed strongly altered MEL secretion. This secretion was continuous during the period of sampling, without any characteristic nocturnal peak. Nevertheless, one month after surgery, a nocturnal increase in melatonin secretion synchronized with the dusk was again observed, but the duration of the melatonin secretion was longer than the duration of the night.These results confirm that the SCN mediates the nocturnal pineal gland activity, demonstrate that the anterior part of the sheep SCN is the main drive for the inhibition of the melatonin secretion at dawn and suggest that a positive input to the pineal gland may stimulate MEL secretion at dusk. The partial recovery of the cyclic secretion of melatonin after complete lesioning of the SCN suggests the existence of other structure(s) involved in this rhythmic function.

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00677.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractPharmacogerietically selected Wistar rat lines were used to investigate the implication of either high or low responsiveness of the dopamine system for the activity of the hypothalamus‐pituitary‐adrenal (HPA) axis. As selection criterion the gnawing response induced by the dopamine agonist apomorphine was used. This criterion allows to distinguish apomorphine susceptible (apo‐sus) rats which show a vigorous gnawing response from apomorphine unsusceptible (apo‐unsus) rats. The present study, using male animals of the 9‐1 2th generation of the two rat lines, revealed the following characteristics of the stress response system: (i) in apo‐sus rats under basal conditions corticotrophin‐releasing hormone (CRH) mRNA level in the paraventricular nucleus (PVN) and plasma adrenocorticotropin (ACTH) concentration were significantly higher; total corticosterone (B) plasma level was similar but free B level was lower; (ii) exposure to a novel environment resulted in a higher and prolonged plasma ACTH and total B response in the apo‐sus rats. Moreover, the elevated free B level was also prolonged; (iii) apo‐sus rats had increased CRH‐induced pituitary ACTH release and B secretion was also increased, but not as prolonged as during novelty. (iv) In dexamethasone‐pretreated rats an intravenous ACTH1–24injection resulted in a similar plasma B response in rats of both lines; (v) In vitro, ACTH1–24produced a significantly higher B secretion by adrenocortical cells of apo‐sus rats reflecting the higher in vivo ACTH priming of the adrenal glands in these animals. (vi) apo‐sus rats had higher body and thymic weight.In conclusion, rats genetically selected for increased susceptibility of the dopamine system to apomorphine display subtle adrenocortical hyporesponsiveness and show resistance to corticost

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00678.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0953-8194    

DOI:10.1111/j.1365-2826.1995.tb00679.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY