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Biomedical subjects

P V Holmes

Publications and source records attributed to P V Holmes.

At least 19 recordsLinked to original sources
PubMed1995

Lack of effect of chronic morphine treatment and naloxone-precipitated withdrawal on tyrosine hydroxylase, galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus.

Morphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days. Withdrawal was precipitated in half of the morphine-dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal were evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropeptide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone-precipitated withdrawal. In contrast, mRNA levels for c-fos were dramatically elevated in the LC following naloxone-precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing factor (CRF) in Barrington's nucleus. Although long-term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process.

Animals↗
PubMed1995

Chronic social stress increases levels of preprogalanin mRNA in the rat locus coeruleus.

Galanin is a 29 amino acid neuropeptide that coexists with norepinephrine in approximately 80% of locus coeruleus (LC) neurons in the rat. The effects of chronic, naturalistic stress on preprogalanin mRNA in the LC was studied. The visible burrow system (VBS) served as the stress paradigm. Long-Evans rats (three males and two females) were housed together in the VBS for 13 days. The males established dominance hierarchies during this period. On day 14, preprogalanin mRNA in the LC was significantly elevated in subordinate rats compared to dominant and control rats, as measured by quantitative in situ hybridization. Levels of mRNA were positively correlated with the number of wounds by day 7 and day 14 and negatively correlated with body weight gain by day 14. These results suggest that the neuropeptide galanin may be overexpressed during chronic stress in rats.

Animals↗
PubMed1995

Environmentally induced changes in peripheral benzodiazepine receptors are stressor and tissue specific.

The stress-induced changes in peripheral benzodiazepine receptors (PBR) can be observed in a number of different tissues, depending upon the nature and chronicity of the aversive experience. In addition, virtually all stress procedures that cause rapid changes in PBR simultaneously increase the physical activity or metabolic rate of the subjects. The present study analyzed the contributions of rapid alterations in activity or metabolic rate with and without aversive stimulation and their subsequent impact on PBR. Mechanically induced increases in activity by forced running stress results in a significant reduction in [3H]Ro 5-4864 binding to PBR in olfactory bulb, opposite to the PBR changes in this tissue following forced cold-water swim stress. Pharmacological induction of increased locomotor activity as well as metabolic rate by d-amphetamine causes a significant increase in cardiac PBR binding, again, opposite to the response typically observed following inescapable shock stress. Finally, administration of the anxiogenic beta-carboline, FG-7142, causes increases in both hippocampus and adrenal gland PBR binding reminiscent of acute noise stress exposure. These experiments demonstrate that increased locomotor activity or metabolic rate alone is not a necessary and sufficient condition for previous stress-induced changes in PBR. Conversely, increased metabolic rate coupled with an aversive stimulus appears to be an important factor for inducing stress-like changes in PBR. This data, coupled with previous reports, suggests that rapid alterations in these sites are stressor and tissue dependent. Finally, we propose that the PBR may be involved in many aspects of the stress response including: a) a blowarning system in adrenal gland, b) participation in stress-induced hypertension via renal PBR, and c) a modulator of stress-induced immunosuppression and subsequent recovery of function or recuperation by actions on immune cells.

Animals↗
PubMed1994

Intraventricular administration of galanin does not affect behaviors associated with locus coeruleus activation in rats.

The 29 amino acid peptide galanin (GAL) coexists with norepinephrine in rat locus coeruleus (LC) neurons to a remarkably high degree. The effects of central administration of GAL were examined in three behavioral paradigms that putatively involve increases in the activity of LC neurons. GAL did not affect behavioral signs associated with naloxone-precipitated withdrawal in rats treated chronically with morphine, a condition in which the firing rate of LC neurons is dramatically increased, although the behavioral signs of withdrawal were abolished by clonidine. Foot shock induced freezing behavior was similarly unaffected by either dose of GAL but was significantly diminished by clonidine and the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF. GAL did not influence the decrease in exploratory activity in a novel open field induced by idazoxan. The behavioral activity of the peptide and route of administration were confirmed in a feeding paradigm. Doses of GAL that were inactive in the three paradigms were active in stimulating intake of a palatable food to a similar degree as clonidine-stimulated intake. These results suggest that intraventricularly administered GAL may not influence behaviors thought to be mediated by activation of neurons in the LC.

Animals↗
PubMed1993

Amygdaloid central nucleus lesions and cholinergic blockade attenuate the response of the renal peripheral benzodiazepine receptor to stress.

Previous research has demonstrated that the density of peripheral benzodiazepine receptors (PBR) in rat kidney rapidly drops following exposure to 80 min of stress. The present experiments examined the contribution of the central and autonomic nervous systems in mediating this effect. Ibotenic acid lesions of the amygdaloid central nucleus (ACe), but not the lateral and basolateral amygdala, diminished the magnitude of the reduction in renal PBR binding caused by stress. Pretreating rats with methyl-scopolamine also inhibited the response of the PBR to stress. Adrenergic blockade with nadolol was ineffective. In order to test whether the PBR was under direct or indirect neural control during stress, unilateral renal denervation was performed. The stress-induced reduction in PBR binding persisted in denervated kidneys revealing that any neural control over the PBR that might exist must be indirect. Together the results suggest that the CNS may be involved in regulating the PBR during stress through the activation of intermediate, possibly hormonal, factors. The involvement of the central nervous system in the modulation of the PBR indicates the relevance of the PBR to physiological adaptations to stress.

Acetylcholine↗
PubMed1993

Etiology of the sexual dimorphism in renal peripheral benzodiazepine receptor response to stress in rats.

A sexual dimorphism in stress-induced alterations in renal peripheral benzodiazepine receptors (PBR) was recently reported. The present paper includes five experiments examining the etiology of this sex difference. Surgical removal of ovaries and testes was ineffective in altering the renal PBR stress response in both male and female rats. A diurnal variation in the sexual dimorphism was observed; the difference was seen in the early part of the light cycle, while the two sexes were indistinguishable at the end of the light cycle. Finally, based on recent data indicating the importance of the renin-angiotensin system in the stress-induced decrease in renal PBR, we examined both stress-induced plasma renin activity and renal PBR reactivity to exogenous angiotensin II (AII) administration in both sexes. Female rats show both an attenuated elevation of plasma renin levels in response to inescapable shock stress and a reduced PBR response to AII administration in comparison to males. The present data indicate that the renin-angiotensin system may be a critical factor in the sexual dimorphism in the renal PBR response to stress. The possibility of this difference in the renin-angiotensin system contributing to sex differences in susceptibility to escape deficits following inescapable shock is entertained. The implications for these findings regarding the physiological function of the PBR are also discussed.

Angiotensin I↗
PubMed1993

Embryonic stem cells express growth hormone receptors: regulation by retinoic acid.

Embryonic and fetal growth are generally considered to be independent of pituitary GH. However, it has been demonstrated recently that 18-day-old rat embryos and rat fetuses express GH receptors, suggesting that GH could play a role in early development. The aim of the present investigation was to determine whether preimplantation embryos also express GH receptors. Germ line competent mouse embryonic stem (ES) cells and cultured mouse preimplantation embryos were examined with Northern blot analysis, RNAse-protection solution-hybridization assays, reverse transcription/polymerase chain reaction assays and immunohistochemistry for the detection of GH receptors. Northern blot analysis of ES cells using a probe corresponding to the extracellular domain of the GH receptor demonstrated the presence of two transcripts (1.2 and 4.5 kilobases). The RNAse-protection solution-hybridization assay revealed that ES cells express approximately one sixth of the GH-receptor messenger RNA (mRNA) levels expressed in liver from pregnant mice. Treatment of cultured ES cells with retinoic acid (100 nM) for 6 days increased GH-receptor mRNA levels (P < 0.01). GH-receptor mRNA was further identified in ES cells, preimplantation embryos, muscle, liver, and placenta by a reverse transcription/polymerase chain reaction assay. In humans it has previously been shown that exon 3 of the GH-receptor is deleted in the placenta. However, none of the studied mouse tissues had a deletion of the GH-receptor mRNA corresponding to exon 3 of the human GH receptor. GH-receptor immunoreactivity was identified on the cultured ES-cells by immunohistochemistry. In conclusion, we have in the present study shown that germline competent ES cells and preimplantation mouse embryos express the GH receptor transcript and that this transcription is increased by retinoic acid in ES cells. Furthermore, the presence of GH-receptor immunoreactivity on the ES cells indicates that the GH-receptor transcript is translated.

Animals↗
PubMed1992

Angiotensin II rapidly modulates the renal peripheral benzodiazepine receptor.

The effects of acute exposure to angiotensin II (AII) on the renal peripheral benzodiazepine receptor were studied in rats. As little as 37.5 micrograms of AII injected s.c. over an 80 min period caused immediate reductions in [3H]Ro5-4864 binding. Scatchard analysis revealed that the reduction in [3H]Ro5-4864 binding induced by AII was due to a drop in receptor density or Bmax. The influence of AII on the peripheral benzodiazepine receptor is similar to that of stress.

Angiotensin II↗
PubMed1992

Impact of psychological dynamics of stress on the peripheral benzodiazepine receptor.

In an attempt to dissociate the relative impact of psychological vs. physiological concomitants of stress on the peripheral benzodiazepine receptor (PBR), the influence of stressor controllability and predictability was investigated in rats. In addition, the effect of a purely psychological stressor, contextually conditioned fear, was examined. The response of the PBR in rats confronted with a naturalistic threat, a cat, was also tested. Various peripheral and CNS tissues were analyzed. Specific binding of [3H]Ro 5-4864 was significantly reduced in the kidneys of subjects receiving either controllable or uncontrollable shock. Similar changes were seen in the kidneys of subjects receiving either predictable or unpredictable shock. Mean [3H]Ro 5-4864 binding in lung was reduced following both predictable and unpredictable shock, but only the reduction in the predictable shock group reached significance. Controllability appeared to protect against the stress-induced reduction in [3H]Ro 5-4864 binding in lung. Contextually conditioned fear only affected PBR in the olfactory bulb, and exposure to a cat was without effect. These data suggest that the PBR responds only to potent stressors, and psychological influences on the PBR are tissue specific.

Animals↗
PubMed1991

Differential effects of anxiogenic central and peripheral benzodiazepine receptor ligands in tests of learning and memory.

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4'-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies.

Animals↗
PubMed1991

Sexual dimorphism of stress-induced changes in renal peripheral benzodiazepine receptors in rat.

Adult male and female rats were exposed to either inescapable shock or no treatment. In vitro [3H]Ro 5-4864 (4'-chlorodiazepam) binding (1 nM) to peripheral benzodiazepine receptors (PRB) in both CNS and peripheral tissues indicated no gender differences in olfactory bulb, heart, lung or adrenal gland but a significant effect was observed in renal tissue. Female rats showed an attenuated stress-induced reduction (23%) in PBR in comparison to males (55%). This difference was shown to be an alteration of Bmax and not kD by Scatchard analysis. These data are the first demonstration of a sexual dimorphism in environmentally-induced alterations in PBR.

Animals↗
PubMed1991

Central and peripheral benzodiazepine receptors: involvement in an organism's response to physical and psychological stress.

The present review discusses the current knowledge of the molecular pharmacology and neuroanatomical and subcellular localization of both the central benzodiazepine/GABA-chloride ionophore receptor complex and the peripheral benzodiazepine receptor. It then reviews all of the literature to date on how these two receptor sites are modulated by environmental stress. The possible role of these sites in learning and memory is also discussed. Finally, a theoretical model is presented which examines the differential, and perhaps complementary, alterations of these two sites in an organism's response to stress.

Animals↗
PubMed1991

Interleukin-1 alpha modulates luteinizing hormone stimulated cyclic AMP and progesterone release from human granulosa cells in vitro.

This study examines the possible direct effect of interleukin-1 alpha (IL-1 alpha) upon human granulosa cells. The cells were isolated from follicles of stimulated cycles in women undergoing oocyte retrieval for in-vitro fertilization. Purified cell preparations were cultured for different time periods in the presence of IL-1 alpha and human luteinizing hormone (LH) or follicle stimulating hormone. IL-1 alpha stimulated basal as well as LH-induced progesterone accumulation. The response in terms of cyclic AMP was more complex, there was no effect of IL-1 alpha on basal cyclic AMP accumulation. However, at the highest concentration tested (50 IU/ml), IL-1 alpha enhanced cyclic AMP accumulation over that seen with LH alone. At a lower concentration, IL-1 alpha either had no effect or was slightly inhibitory to the LH-induced cyclic AMP accumulation, depending on the culture period. Our results, taken together with other findings, are compatible with the view that IL-1 alpha has a potential regulatory role in the granulosa-luteal cell transition in the human ovary.

Cells, Cultured↗
PubMed1991

Platelet-derived growth factor is detected in human blastocyst culture medium but not in human follicular fluid--a preliminary report.

The content of PDGF in human blastocyst culture medium (n = 8), serum (n = 12), and FF (n = 17) from natural IVF cycles was determined by an RIA specific for PDGF B-chain. The blastocysts were cultured under serum-free conditions throughout development. The findings show that PDGF B-chain is released into the culture medium of human blastocysts and that serum is positive, whereas FF is negative for PDGF.

Blastocyst↗
PubMed1990

Pentobarbital blocks the stress-induced decrease in [3H]Ro 5-4864 binding in rat kidney.

Exposure to environmental stress causes changes in the binding of [3H]Ro 5-4864 to peripheral benzodiazepine receptors (PBRs). The influence of the central nervous system (CNS) in these stress-induced modifications is unclear. The present study examined whether pretreatment with a dose-response regimen of sodium pentobarbital would impact the stress-induced reduction in renal PBR. Administration of either a sedative/ataxic (20 mg/kg) or hypnotic (60 mg/kg) dose of pentobarbital prior to stress blocks the stress-induced decrease of [3H]Ro 5-4864 binding to renal PBR in rat. These findings suggest that higher-order, supraspinal mechanisms play a critical role in marshalling the renal PBR changes in response to stress.

Animals↗
PubMed1990

Prostaglandin-E2 released by pre-implantation human conceptuses.

This work investigates the production of prostaglandin E2 (PGE2), a well known modulator for the suppression of immune cells, by pre-implantation human conceptuses from the 4-cell stage to the hatched blastocyst and by cumulus oophorus cells, these being obtained from an IVF/ET program. Cumulus cell complexes cultured for 48 h produced considerable amounts of PGE2, necessitating complete removal of their influence on the conceptus cultures. All stages of the human conceptus studied produced PGE2 during 48-h cultures, the greatest amounts from late blastocysts, and from those cultured in media containing bovine serum albumin rather than human donor serum. Indomethacin-treated control blastocysts confirmed the synthesis and release from the human conceptuses. The production of PGF2a from human blastocysts could not be demonstrated.

Blastocyst↗
PubMed1990

Inhibitors of lipoxygenase increase the ovulation rate in the in-vitro perfused luteinizing hormone-stimulated rabbit ovary.

In order to determine whether leukotrienes, products of the lipoxygenase pathway, are involved in ovulation, pairs of rabbit ovaries were treated with the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and caffeic acid (CA) while being perfused in vitro. The control ovaries from each rabbit received luteinizing hormone (LH) (1.5-2.25 micrograms ml-1) while the contralateral ovaries were treated with LH + NDGA (100 microM) or LH + CA (100 microM). The numbers of ovulations from both the LH + NDGA- and LH + CA-treated ovaries were significantly higher (P less than 0.05) than from their respective LH-stimulated controls. Treatment with NDGA alone in the perfusate did not cause any ovulation, while CA alone caused one ovulation from one of six ovaries perfused. Ovarian tissue levels of prostaglandins after 7 h of perfusion with LH + NDGA or with LH alone showed that, in five of the six ovaries perfused in this group, the tissue levels of PGE2, 6-keto-PGF1 alpha and PGF2 alpha were higher in the presence of NDGA. The mean differences were significant (P less than 0.05) for prostacyclin but not significant (P greater than 0.05) for PGE2 and PGF2 alpha. Our interpretation of the findings is that, when used for blocking the lipoxygenase pathway, NDGA and CA increase the substrate availability for the cyclo-oxygenase pathway of arachidonic acid metabolism, resulting in a net increase in prostaglandins. The increased ovarian levels of prostaglandins, especially prostacyclin, may cause the observed increase in ovulation rate. Consequently, although the leukotrienes may be involved in the mechanism of ovulation in the rabbit, their effects appear to be less pronounced than those of prostaglandins.

Animals↗