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C H Walker

Publications and source records attributed to C H Walker.

At least 37 records · Page 2Linked to original sources
PubMed1997

Thyrotropin releasing hormone analog TA-0910 suppresses alcohol intake in alcohol drinking African green monkeys.

In previous studies, we found that single injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake and preference in alcohol-preferring (P) and Fawn-Hooded (FH) rats over a 24-hr period of continuous access to alcohol and water. However, several consecutive daily injections of TA-0910 resulted in the development of tolerance to these effects. In the present study, we found that in a 5-hr limited-access schedule in which monkeys could select an aqueous alcohol solution (7.5% v/v) or tap water, single doses of TA-0910 (0.0625, 0.125, 0.25, 0.5, and 0.75 mg/kg), similar to those found effective in P and FH rats, reduced consumption of alcohol. In this protocol, tolerance to the attenuating effects of TA-0910 on alcohol intake was not evident after five consecutive once-daily doses of 0.5 mg/kg. Furthermore, it was shown that a single dose of 0.75 mg/kg TA-0910 did not significantly influence 24-hr water intake when water was the only available fluid, but did reduce the intake of a preferred solution of saccharin. These findings suggest that activation of brain thyrotropin-releasing hormone systems reduces alcohol intake in primates and that tolerance to this effect is not evident within 5 days under a limited access schedule.

Alcohol Drinking↗
PubMed1997

Involvement of dopamine D2 receptors in the suppressive effect of the thyrotropin-releasing hormone analog TA-0910 on alcohol intake in alcohol-preferring rats.

Pharmacological experiments were conducted to determine the neuronal mechanisms involved in the suppressive effects of the thyrotropin-releasing hormone analog TA-0910 on alcohol intake in alcohol-preferring (P) rats. We previously reported that single intraperitoneal injections of TA-0910 dose-dependently reduced alcohol intake in P rats without altering fluid or total calorie intake; however, after several consecutive, once-daily injections, P rats developed tolerance to the suppressive effects of TA-0910 on alcohol intake and cross-tolerance to like effects of the dopamine D2 agonist bromocriptine, but not to like effects of the serotonin uptake inhibitor fluoxetine. In the present study, rats were injected with vehicle or different doses of the D2 antagonist s(-)-eticlopride (0.01 to 0.05 mg/kg) or the D1 antagonist R(+)-SCH23390 (0.1 to 0.5 mg/kg) and 20 min later with TA-0910 (0.75 mg/kg). Alcohol and water intakes were measured at 2, 4, 6, and 24 hr, and food was measured every 24 hr. Both s(-)-eticlopride and R(+)-SCH23390 produced modest reductions in alcohol intake alone; however, only s(-)-eticlopride antagonized the suppressive effect of TA-0910 on alcohol intake. In related experiments, it was confirmed that the dopamine D3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin reduced alcohol intake in P rats, and it was found that tolerance to this effect did not develop during or after seven consecutive once-daily injections. Furthermore, this effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin was not diminished in rats made tolerant to the effect of TA-0910 on alcohol intake. These data, those of previous studies, and recent preliminary findings support involvement of dopamine D2, but not D1 or D3 receptors in mediating the suppressive effect of TA-0910 on alcohol intake of P rats.

Alcohol Drinking↗
PubMed1996

Effects of prochloraz and malathion on the red-legged partridge: a semi-natural field study.

A semi-natural field study was carried out to assess the likelihood of a potentiation of toxicity between the ergosterol biosynthesis inhibiting (EBI) fungicide, prochloraz, and the organophosphorus (OP) insecticide, malathion, in the red-legged partridge (Alectoris rufa). Groups of partridges kept in four large grassland enclosures were exposed to either prochloraz-treated or control wheat for 7 days after which two of the enclosures were sprayed with malathion whilst the remaining two were sham-sprayed. Cytochrome P-450, aldrin epoxidase and 7-ethoxyresorufin-O-deethylase (EROD) activities were found to be significantly higher in the group exposed to prochloraz alone compared to controls, suggesting that induction of the hepatic microsomal monooxygenase system had occurred by ingestion of prochloraz-treated wheat. However, the level of induction produced was not sufficient to cause a potentiation of malathion toxicity. There was evidence for induction of several forms of P-450 recognised by antibodies raised against 1A1, 2C6 and 4A1 in the prochloraz-exposed partridges.

Journal Article↗
PubMed1996

Analogies between oxytocin systems of the uterus and brain.

In this brief review we have compared OT systems in the brain with those of the uterus and ovary particularly with respect to interactions with steroids. We have presented evidence of heterogeneous OTR and 125I-P-3-BSA binding sites in the MPOA as well as evidence of extensive interactions of steroids and OT in the MPOA, that cannot be adequately explained by genomic effects of steroids. We also discuss a putative analogue between steroid control of OTR stimulation of intracellular calcium levels, phospholipase C activity and prostaglandins in the uterus and steroid effects on OT systems in brain. We have developed a model for steroid control of both OT release and OTR in which we suggest that steroids and OT bind to membrane receptors coupled to G proteins. This model may prove useful in understanding the interactive central actions of steroids and OT systems in regulating the endocrinology and behaviors associated with reproduction.

Animals↗
PubMed1996

Estradiol conjugated to BSA releases oxytocin from synaptosome-containing homogenates from the medial preoptic area-hypothalamus.

Estradiol conjugated to bovine serum albumin at position 6(E-6-BSA) released oxytocin (OT) from homogenates of the medial preoptic area and medial hypothalamus (MPOA-MH) within minutes of its superfusion. Using a superfusion system in which synaptosome-containing homogenates were layered onto acrodiscs maintained at 37 degrees C, we have found that E-6-BSA (100 ng/microliters) superfusions significantly elevated OT release within minutes. In contrast, superfusion of the same concentration of BSA or progesterone-3-BSA (P-3-BSA) had no effect on OT release. While superfusing homogenates with augmented levels of K+ had no effect on OT release itself, superfusing E-6-BSA with these concentrations of K+ consistently increased OT release. This is the first demonstration that E-6-BSA increases OT release in a nucleus-free medium.

Animals↗
PubMed1995

Biochemical biomarkers in ecotoxicology--some recent developments.

Biochemical biomarkers measure the exposure of organisms to environmental chemicals. They can also provide measures of toxic effect, e.g. where they are based on molecular mechanisms which underly toxicity. Ideally, biomarkers should be sensitive, specific, simple to use and suitable for the assay of material obtained by non-destructive sampling procedures (e.g. of blood). Recently, there has been encouraging progress in the development of several different types of biomarker assays: (1) The measurement of inhibition of serum 'B' esterases to monitor exposure of birds to organophosphorus insecticides. (2) The measurement of DNA damage caused by aromatic hydrocarbons. DNA adduct formation has been studied using the 32P-postlabelling technique. Several other techniques are currently under investigation. (3) The measurement of disturbances to the transthyretin-retinol binding protein complex caused by a metabolite of 3,4,3',4',tetrachlorobiphenyl. (4) The measurement of precursors of clotting proteins in blood following the inhibition of the Vitamin K cycle by anticoagulant rodenticides. Of these examples, the first is only a biomarker of exposure but the remaining three examples are, in principle, biomarkers of toxic effect since they all represent measures of molecular mechanisms which underly toxicity. Biochemical biomarkers have considerable potential for measuring effects of chemicals under field conditions--especially where carefully selected combinations of them are used.

Animals↗
PubMed1995

Characterization of progesterone-3-[125I-BSA] binding sites in the medial preoptic area and anterior hypothalamus.

In this study we utilized radiolabeled progesterone (P) conjugated to bovine serum albumin (BSA) at position 3 (P-3-[125I-BSA]) to examine steroid receptors in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVXed) rats. In the MPOA-AH binding of P-3-[125I-BSA] was linear across a tissue concentration range of 0.005 to 0.02 mg protein/0.1 ml of membrane suspension. Kinetic experiments revealed an association t(1/2) of 51.4 min and a dissociation t(1/2) of 122.5 min for P-3-[125I-BSA] at 0 degrees C. Analysis of data from competition binding experiments using P-3-BSA revealed high- and low-affinity binding sites in the MPOA-AH. Involvement of MPOA-AH binding sites with a G-protein was suggested by a reduction of P-3-[125I-BSA] binding in the presence of the non-hydrolyzable GTP analog GTPgammaS but not ATPgammaS. In addition, if homogenates from the MPOA-AH were preincubated with 10(-5) M of the G-protein antagonist cholera toxin for 30 min at 37 degrees C, competition binding data indicated only high-affinity binding sites. Once daily injections of OVXed rats with 4 mg P for 12 days significantly increased the density of P-3-[125I-BSA] binding sites in the MPOA-AH. This treatment did not affect P-3-[125I-BSA] binding in the dorsal tectum, medial basal hypothalamus, ventral tegmental area or the thymus.

Albumins↗
PubMed1994

Neonatal stress transiently alters the development of hippocampal oxytocin receptors.

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.

Animals↗
PubMed1994

Estrogen increases affinity of oxytocin receptors in the medial preoptic area-anterior hypothalamus.

Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not.

Animals↗
PubMed1993

Purification and immunological characterization of pigeon serum butyrylcholinesterase. Implications on environmental monitoring and toxicological testing of birds.

Butyrylcholinesterase (EC 3.1.1.8) (BChE) was purified from pigeon serum to electrophoretic homogeneity by a four-step procedure involving blue sepharose CL-6B chromatography, ion exchange chromatography, procainamide affinity chromatography and gel filtration. An overall 2789-fold purification was achieved, with a final specific activity of 61.35 mumol/min/mg. The purified enzyme separated into two peaks when filtered through a column of Sephacryl S-300, a smaller peak containing the tetrameric form of BChE (C4) and a larger peak containing the monomeric form of BChE (C1). Native polyacrylamide gel electrophoresis (PAGE) of both peaks revealed single protein bands which coincided with esterase activity, with approximate M(r) values of 84,000 and 340,000, respectively. The C1 monomer represented 85-90% of the activity found in the pigeon serum. It is not clear whether this polymorphism of BChE in vertebrates contributes to the wider inter-individual variations observed in xenobiotics elimination kinetics and in the response to the pharmacological and toxic effects of pesticides. PAGE of the monomeric form of the enzyme in the presence of sodium dodecyl sulphate showed only one protein band with a M(r) of 84,000, while that of the tetrameric form revealed two bands, a major protein band (84,000) and a minor band (170,000), representing the monomer and the dimer of the dissociated tetrameric BChE enzyme under reducing conditions. Highly specific polyclonal antibodies were raised in rabbits against the purified enzyme. These antibodies cross-reacted with other avian BChEs, a criterion which make them useful for the immunopurification of other BChEs from different species as well as for biomonitoring and toxicological studies on the role of esterases as an indicator of avian exposure to organophosphorous pesticides.

Animals↗
PubMed1993

Effects of concurrent subchronic treatments with desmethylimipramine and propranolol on beta-adrenergic and serotonin2 receptors in rat brain.

The effects of seven consecutive daily injections of desmethylimipramine (DMI 20 mg/kg) and propranolol (PRO 10 mg/kg) on 3H-dihydroalprenolol (3H-DHA) and 3H-ketanserin (3H-KET) binding in rat brain were examined. Analyses of saturation binding data using the iterative, nonlinear curve-fitting program LIGAND revealed that PRO increased, while DMI reduced, 3H-DHA binding site density in cerebral cortex without altering receptor affinity, as previously reported. DMI reduced 3H-KET binding site density without changing affinity, and PRO produced the same effect. In cerebral cortex and probably in hippocampus and striatum, DMI and PRO administered together increased the density of 3H-DHA binding sites (beta-adrenergic receptors) and reduced their affinity. This combination of drugs reduced the density of 3H-KET binding sites (5-HT2 receptors) in cerebral cortex, but did not change their affinity. These findings indicate a need for additional studies on the interactions of DMI and PRO and related drugs because of implications for the treatment of depressed patients with cardiovascular disorders.

Animals↗
PubMed1993

The classification of esterases which hydrolyse organophosphates: recent developments.

In the IUB classification of 1984, enzymes which hydrolyse paraoxon and other organophosphorous triesters were included in the category of arylesterases--enzymes which hydrolyse phenylacetate (EC 3.1.1.2). With the discovery that some forms of paraoxonase do not hydrolyse phenylacetate, a new entry was made in the revised classification of 1989, Aryldialkylphosphatase (EC 3.1.8.1) under phosphoric triester hydrolases (EC 3.1.8), to distinguish these enzymes from arylesterases. Also some enzymes that hydrolyse phenylacetate do not hydrolyse paraoxon, whereas other enzymes do. Additionally, there is growing evidence for the existence of a number of enzymes which hydrolyse P-F or P-CN bonds of organophosphorous diesters e.g., the nerve gases tabun and soman. These enzymes are in effect organophosphorous acid anhydrolases, and it has been proposed that the earlier entry of (EC 3.8.2.1) now be deleted, and a new entry diisoprophylfluorophosphatase (EC 3.1.8.2) put in its place. Within this category, there is evidence of several enzymes showing different substrate specificities, and different requirements for divalent cations as cofactors, which presents further problems of classification and nomenclature.

Esterases↗
PubMed1993

Sexual activity decreases oxytocin receptor densities in the thymus.

Sexual interactions have multiple effects on oxytocin systems in the brain. In the present study we observed that allowing estrogen-progesterone treated ovariectomized rats to be mounted ten times by a male significantly decreased the density (beta max) of thymic oxytocin receptors. Animals were ovariectomized and after recovery injected once daily for three consecutive days with 0.5 microgram estradiol benzoate (EB) followed by an injection of 500 micrograms progesterone on the fourth day 4-5 hr before testing. They were either placed in a cage with a sexually-active male until mounted ten times (mounted) or were briefly placed in the cage and removed before being mounted (unmounted). Both groups were then killed and their thymuses aseptically removed. Computerized analysis of saturation binding data showed that the densities of oxytocin receptors from mounted animals were significantly (p < 0.02) lower than those of unmounted controls (beta max for unmounted animals = 8.45 +/- 0.84 fmol/mg protein; and for mounted rats = 5.5 +/- 0.33 fmol/mg protein; t6 = 3.23). The possibility is discussed that sexual activity reduces thymic oxytocin receptors which may alter immune responsiveness to sexually-transmitted diseases.

Animals↗
PubMed1993

Effects of thyroid state on preference for and sensitivity to ethanol in Fischer-344 rats.

1. It has been reported by several groups that thyroid status can alter ethanol preference in rats. However, results using different methods and different strains of rats have not been consistent. 2. In this study, thyroidectomy or T4 augmentation was used to produce hypothyroidism or hyperthyroidism, respectively, in adult male Fischer-344 rats. 3. Preference for weak solutions (4 or 5%) of ethanol or tap water and ethanol-induced sedation and hypothermia were compared in hypothyroid, hyperthyroid and euthyroid rats. 4. No significant differences in preference indices (the ratios of ethanol to total liquid consumed) among the three groups were observed; however, for ethanol to contribute a greater portion of total calories ingested by hypothyroid rats than by euthyroid or hyperthyroid rats. 5. The duration of sleep resulting from a single i.p. injection of 2.5 mg/kg ethanol was increased (by 34%) in hyperthyroid rats and decreased (by 16%) in hypothyroid rats compared to euthyroid controls. Only the effect of hyperthyroidism was significant at the 0.05 level. 6. Colonic temperatures differed with thyroid state (hyperthyroid > euthyroid > hypothyroid) but the decrease produced by ethanol did not differ by thyroid state. 7. Observed differences in ethanol-induced sedation are consistent with differences in brain TRH levels and effects on neurotransmitter systems associated with different thyroid states.

Alcohol Drinking↗
PubMed1993

L-triiodothyronine: is this peripheral hormone a central neurotransmitter?

L-triiodothyronine (T3) has previously been shown to enhance fast-phase, depolarization-induced 45Ca uptake and 3H-gamma-aminobutyric acid release by rat brain synaptosomes at low nanomolar concentrations comparable to those reported for whole brain. Nevertheless, the physiologic importance of these nonnuclear-mediated effects of T3 has remained uncertain, in part because specific mechanisms and the presence of T3 at presumptive sites of action have not been demonstrated. Isotopic studies showing that L-tetraiodothyronine (thyroxine T4) and T3 are concentrated in synaptosomes, and that T4 is deiodinated to T3 suggested that endogenous levels of T3 in nerve terminals are probably much higher than in other compartments of the brain. In the present study we confirmed that endogenous levels of T3 in nerve terminals are at least eightfold higher, and may be as much as 60-fold higher, than in whole brain. More importantly, we showed that both 125I-labeled T3 and endogenous T3, but not 125I-T4 or endogenous T4, are released from depolarized synaptosomes, primarily by a Ca(2+)-dependent process. This demonstrates a mechanism for raising the level of T3 within the synapse, where the hormone may interact with pre- and postsynaptic binding (or uptake) sites, and suggests that the peripheral hormone T3 may be a neurotransmitter.

Animals↗