Discriminative stimulus effects of 8-hydroxy-2-(di-n-propylamino)tetralin in pigeons and rats: species similarities and differences

S. E. Snodgrass (1985, 1992) examined interpersonal sensitivity within status-discrepant interactions. Using the correlation between how a participant thought another felt with how that person reported actually feeling, S. E. Snodgrass's measure of interpersonal sensitivity included both the expressivity of one person and the perceptivity of another person. The studies reported here were conducted to clarify the relative contributions of expressivity and perceptivity to this measure. Results indicated that interpersonal sensitivity was associated more with high expressivity on behalf of the sender than with the perceiver's perceptivity. Implications are discussed for research and theory on interpersonal sensitivity, and gender and leadership roles.     

Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n- propylamino)tetralin in the rat

The role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated by using the shock titration test in rats. A subcutaneous injection of 300 micrograms/kg 8-OH-DPAT significantly raised the threshold for flinching, jumping and vocalization whereas 100 micrograms/kg only inhibited the flinch response. l-Propranolol and (+)-[N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl propanamide dihydrochloride], (+)-WAY100135, two antagonists at 5-HT1A receptors at 10 mg/kg s.c. antagonized the effect of 300 micrograms/kg 8-OH-DPAT on all measures. The effect of 300 micrograms/kg 8-OH-DPAT on the three measures was unmodified in rats which had received 150 micrograms 5,7-dihydroxytryptamine intracerebroventricularly 10 days before testing. The results suggest that 8-OH-DPAT inhibits nociceptive responses by stimulating postsynaptic 5-HT1A receptors.     

Cardiovascular and sympathetic effects of proadrenomedullin NH2-terminal 20 peptide in conscious rats

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are derived from the same gene, are novel vasodilative peptides and have been shown to exhibit hypotensive action in anesthetized animals. To avoid the modification via anesthesia, we investigated the effects of intravenously administered PAMP on mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) relative to those of AM in conscious unrestrained rats. We also examined whether the arterial baroreceptor reflex was altered with the two peptides. Intravenous injection of rat PAMP (rPAMP) (10, 20 and 50 nmol/kg) and rat AM (rAM) (0.3, 1.0 and 3.0 nmol/kg) similarly elicited dose-related hypotension accompanied by increases in HR and RSNA. However, the responses to rPAMP were less potent in magnitude and shorter in duration than those to rAM. Moreover, rAM facilitated baroreflex control, whereas rPAMP attenuated it. These findings indicate that although PAMP, as well as AM, may play an important role as a circulating hormone in the systemic circulation of conscious rats, the two peptides derived from an identical origin might have different mechanisms responsible for their cardiovascular and RSNA actions.     

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.     

Cardiovascular effects of oxymetazoline and UK14,304 in conscious and pithed rats

Relatively selective alpha 2-adrenoceptor agonists have proven useful in a variety of therapeutic situations including hypertension, glaucoma and withdrawal from opiate addiction. In particular, oxymetazoline (OXY) and UK14,304 (UK) have been used in subclassifying alpha 2-adrenoceptors and imidazoline receptors. We evaluated the cardiovascular effects of OXY and UK in conscious and pithed rats in the presence and absence of efaroxan (EFA), idazoxan (IDA) and rauwolscine (RAU). Both OXY or UK (1, 5 and 10 micrograms/kg, i.v.) increased blood pressure (BP) and reduced heart rate (HR) in conscious rats. In pithed rats, OXY and UK each increased BP to a greater extent than that observed in conscious rats, but HR was not affected. BP increases following sympathetic nerve stimulation in the pithed rats were not affected by OXY but were reduced by UK at 0.1 Hz and 0.3 Hz. HR responses to nerve stimulation in pithed rats were reduced after OXY at all frequencies, but only at 0.1 Hz following UK. EFA, IDA and RAU inhibited the pressor responses of UK, with EFA being most potent. OXY-induced pressor responses were inhibited by all three antagonists, RAU being the least potent. HR responses to either OXY or UK were not affected by the antagonists. Taken together, the data suggest that: 1) alpha 2-adrenoceptors contribute less to the vascular response to OXY than to UK based upon the antagonistic effect of RAU; 2) prejunctional I1 receptors maybe more prevalent in the heart than in vascular tissue based upon the response to OXY in pithed rats. Thus, the heterogeneity among receptors mediating cardiac and vascular responses are complex.     

Differential regulation of somatodendritic serotonin 5-HT1A receptors by 2-week treatments with the selective agonists alnespirone (S-20499) and 8-hydroxy-2-(Di-n-propylamino)tetralin: microdialysis and autoradiographic studies in rat brain

Single treatment with the serotonin (5-hydroxytryptamine) 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and alnespirone (S-20499) reduces the extracellular 5-HT concentration (5-HText) in the rat midbrain and forebrain. Given the therapeutic potential of selective 5-HT1A agonists in the treatment of affective disorders, we have examined the changes in 5-HT1A receptors induced by 2-week minipump administration of alnespirone (0.3 and 3 mg/kg/day) and 8-OH-DPAT (0.1 and 0.3 mg/kg/day). The treatment with alnespirone did not modify baseline 5-HText but significantly attenuated the ability of 0.3 mg/kg s.c. alnespirone to reduce 5-HText in the dorsal raphe nucleus (DRN) and frontal cortex. In contrast, the ability of 8-OH-DPAT (0.025 and 0.1 mg/kg s.c.) to reduce 5-HText in both areas was unchanged by 8-OH-DPAT pretreatment. Autoradiographic analysis revealed a significant reduction of [3H]8-OH-DPAT and [3H]WAY-100635 [3H-labeled N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexa necarboxamide x 3HCl] binding to somatodendritic 5-HT1A receptors (but not to postsynaptic 5-HT1A receptors) of rats pretreated with alnespirone but not with 8-OH-DPAT. In situ hybridization analysis revealed no change of the density of the mRNA encoding the 5-HT1A receptors in the DRN after either treatment. These data indicate that continuous treatment for 2 weeks with alnespirone, but not with 8-OH-DPAT, causes a functional desensitization of somatodendritic 5-HT1A receptors controlling 5-HT release in the DRN and frontal cortex.     

Sleep induction by microinjection of pentobarbital into the medial preoptic area in rats

In a previous study we have shown that microinjection of the benzodiazepine hypnotic triazolam into the medial preoptic area increases sleep in rats. In order to determine whether this effect is specific to benzodiazepines, or whether it occurs with hypnotic medications from other pharmacologic classes, we have microinjected pentobarbital (1 and 100 micrograms) and vehicle in random sequence into rats and performed two hour sleep studies in the daytime with the lights on. Both doses significantly decreased sleep latency and increased nonREM and total sleep. The amount of REM sleep, REM latency, and intermittent waking time were not significantly altered. These data are consistent with the hypothesis that the medial preoptic area may be involved in sleep induction by both benzodiazepine and barbiturate hypnotic medications.     

Enantioselective high-performance liquid chromatography assay of (+)R- and (-)S-alpha-lipoic acid in human plasma

The Epstein-Barr virus (EBV) genome was detected by polymerase chain reaction (PCR) in mononuclear cells from bone marrows with diverse types of hematopoietic malignancies. Viral repeated sequences (BamHI-W region) were detected in 42 of 82 (51%) hematopoietic malignancies, including polycythemia vera, but not in nonneoplastic cases. EBV-positive cases were found to consist of various histological types. We did not detect any EBV PCR product in the peripheral blood. The EBV BamHI-Y, -H region, encoding EBV nuclear antigen 2 DNA, which is a single-copy gene in the viral genome, was detected in only 13 of 42 BamHI-W-positive cases, suggesting that the copy number of the EBV genome differed in each case. In all cases, the PCR band was verified by Southern blot hybridization using specific EBV probes. Whether the infected virus is an etiologic agent of the malignancy or merely a latent infection cannot be determined by the PCR assay performed under these conditions. These results, however, suggest that a novel form of EBV latent infection is present in the bone marrow of patients with hematopoietic malignancies.     

8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats

The effect of phospholipase C treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with phosphatidylcholine-specific Clostridium welchii phospholipase C reduced the pool size of phosphatidylcholine compared with controls whereas the pool size of cardiolipin and phosphatidylglycerol were unaffected. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or pre-incubated in the absence or presence of phospholipase C. In all experiments, radioactivity incorporated into cardiolipin and phosphatidylglycerol were reduced in phospholipase C-treated cells with time compared with controls indicating attenuated de novo biosynthesis of these phospholipids. Addition of 1,2-dioctanoyl-sn-glycerol, a cell permeable 1,2-diacyl-sn-glycerol analog, to cells mimicked the inhibitory effect of phospholipase C on cardiolipin and phosphatidylglycerol biosynthesis from [1,3-3H]glycerol indicating the involvement of 1,2-diacyl-sn glycerol. The mechanism for the reduction in cardiolipin and phosphatidylglycerol biosynthesis in phospholipase C-treated cells appeared to be a decrease in the activities of phosphatidic acid:cytidine-5'triphosphate cytidylyltransferase and phosphatidylglycerolphosphate synthase, mediated by elevated 1,2-diacylsn-glycerol levels. Upon removal of phospholipase C from the incubation medium, phosphatidylcholine biosynthesis from [methyl-3H]choline was markedly stimulated. These data suggest that de novo phosphatidylglycerol and cardiolipin biosynthesis may be regulated by 1,2-diacyl-sn-glycerol and support the notion that phosphatidylglycerol and cardiolipin biosynthesis may be coordinated with phosphatidylcholine biosynthesis in H9c2 cardiac myoblast cells.     

Isomers of erythro-5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril, a new bronchodilator

The isomers of erythro-5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril (1), a new potent and beta2-selective bronchodilator, were synthesized by optical resolution of compound 1 and inversion of the erythro to the threo isomers. The isomers were tested for activities to inhibit histamine-induced bronchospasm and to increase the heart rate of anesthetized dogs. Racemic and (-)-erythro-1 showed potent and beta2-selective bronchodilater activities. Among the isomers, (-)-erythro-1 showed the highest activities and (+)-erythro-1 showed the lowest.     

Potential anxiolytic properties of R-(+)-8-OSO2CF3-PAT, a 5-HT 1A receptor agonist

The inhibitory effect of 2% ethanol (400 mM) in the incubation medium on several characteristics of the Na(+)-ATPase of basolateral plasma membranes from rat kidney proximal tubular cells was investigated. Ethanol did not change the Km of the enzyme for Mg2+, ATP or Na+; it did not change either the optimal pH or temperature values of the incubation medium for the enzyme to act and finally, it did not affect the apparent energy of activation of the enzyme. It was also found that 2% ethanol produced stronger inhibition of the ATPase when it is in an activated or stimulated state, than when it is working at its lower basal level. The presented results can be explained by assuming that 2% ethanol in the incubation medium inhibits Na(+)-ATPase activity by affecting the enzyme structure as well as its activating mechanism.     

Elevated 8-hydroxy-2'-deoxyguanosine levels in lung DNA of A/J mice and F344 rats treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and inhibition by dietary 1,4-phenylenebis(methylene)selenocyanate

1,4-Phenylenebis(methylene)selenocyanate (p-XSC) is an effective chemopreventive agent against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung adenoma in female A/J mice. While p-XSC can effectively inhibit NNK-induced DNA methylation in female A/J mice and in male F344 rats, its effect on NNK-induced oxidative DNA damage had not been determined. Thus, the effect of p-XSC on the levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in lung DNA from A/J mice and F344 rats treated with NNK was examined. Mice were given NNK by gavage (0.5 mg/mouse in 0.2 ml corn oil, three times per week for 3 weeks) or by a single i.p. injection (2 mg/mouse in 0.1 ml saline) while maintained on a control diet (AIN-76A) or control diet containing p-XSC at 10 or 15 p.p.m. (as Se) starting 1 week before NNK administration and continuing until termination. Mice were killed 2 h after the last NNK gavage in the multiple administration protocol or 2 h after the single i.p. injection. Treatment with NNK by gavage significantly elevated the levels of 8-OH-dG in lung DNA of A/J mice from 0.7 +/- 0.1 to 1.6 +/- 0.2 adducts/10(5) 2'-deoxyguanosine (dG) (P < 0.001), while dietary p-XSC (at 10 p.p.m. Se) prevented significant elevation of the levels of this lesion caused by NNK, keeping them at 0.9 +/- 0.1 adducts/10(5) dG (P < 0.003). Injection of NNK in saline also significantly increased the levels of 8-OH-dG in lung DNA of A/J mice from 1.2 +/- 0.6 to 3.6 +/- 0.8/10(5) dG adducts (P < 0.01), while dietary p-XSC (at 15 p.p.m. Se) kept these levels at 1.9 +/- 0.5 adducts/10(5) dG (P < 0.03). Rats were given a single i.p. injection of NNK (100 mg/kg body wt) in saline while being maintained on control diet (AIN-76A) or control diet containing p-XSC (15 p.p.m. as Se) starting 1 week before NNK administration and continuing until termination. The rats were killed 2 h after injection. Treatment with NNK using this protocol significantly elevated the levels of 8-OH-dG in lung DNA of F344 rats from 2.6 +/- 0.5 to 3.5 +/- 0.5 adducts/10(5) dG (P < 0.03), while dietary p-XSC (at 15 p.p.m. Se) kept the levels of this lesion at 2.2 +/- 0.6 adducts/10(5) dG (P < 0.01). Our findings suggest that the chemopreventive efficacy of p-XSC against NNK-induced lung tumorigenesis in A/J mice and F344 rats may be due in part to inhibition of oxidative DNA damage.     

Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, in rats

The present study was designed to investigate the modifying effects of dietary 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), a new synthetic retinoidal butenolide, during the post-initiation phase on azoxymethane (AOM)-induced rat intestinal carcinogenesis. The number of aberrant crypt foci (ACF) in rat colon, colonic ornithine decarboxylase (ODC) activity and bromodeoxy-uridine (BrdUrd) labeling index in rat colonic epithelium were also assessed. At 7 weeks of age, male F344 rats (except the KYN-54 alone and control groups) were given weekly s.c. injections of AOM at 15 mg/kg body wt for 3 weeks. Starting 1 week after the last injection of AOM, rats (except the control group) were fed a diet containing KYN-54 at concentrations of 100 or 200 p.p.m. throughout the experiment. All animals were necropsied at 32 weeks after the start of the experiment. Compared with the AOM alone group, KYN-54 at both doses reduced the incidence and multiplicity of tumors in entire intestine (small and large intestines). In the 200 p.p.m. KYN-54 fed group especially, tumor incidence and multiplicity in the entire intestine were lower compared with the AOM alone group (P < 0.005 and P < 0.05 respectively). Also, the number of ACF/cm2 colon in the groups of rats treated with AOM and KYN-54 at both doses were significantly lower than that of rats treated with AOM alone (P < 0.05). Colonic ODC activity and BrdUrd labeling index in the groups of rats treated with AOM and KYN-54 at both doses were slightly lower than those treated with AOM alone. KYN-54 at 200 p.p.m. significantly lowered BrdUrd labeling index induced by AOM (P < 0.005). These results suggest that KYN-54 might be a promising chemopreventive agent for intestinal neoplasia.     

Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats

In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.     

Neonatal treatment with tamoxifen causes immediate alterations of the sexually dimorphic nucleus of the preoptic area and medial preoptic area in male rats

We have characterized two different types of Cl- currents in calf pulmonary artery endothelial (CPAE) cells by using a combined patch-clamp and Fura-2 microfluorescence technique to measure simultaneously ionic currents and the intracellular Ca2+ concentration, [Ca2+]i. Exposure of CPAE cells to 28% hypotonic solution induces cell swelling without a change in membrane capacitance and [Ca2+]i, and concomitantly activates a current. This current, I(Cl, vol), is closely correlated with the changes in cell volume and shows a modest outward rectification. It slowly inactivates at potentials more positive than +60 mV but is time- and voltage-independent at other potentials. Increase in [Ca2+]i by different maneuvers, such as application of vasoactive agonists (ATP), ionomycin, or loading of the cells directly with Ca2+ also activates a Cl- current, I(Cl, Ca). This current slowly activates at positive potentials, inactivates quickly at negative potentials and shows strong outward rectification. A time-independent component of the current activated by elevation of [Ca2+]i alone can be inhibited by cell shrinking by exposing the cells to hypertonic solution, indicating that an increase in [Ca2+]i also co-activates I(Cl, vol). Forskolin or cAMP never activated a current in CPAE cells, which indicates the lack of cAMP-activated channels in these cells. There is also no evidence for the existence of voltage-gated Cl- channels in resting, nonstimulated cells. Challenging a cell with elevated [Ca2+]i and hypotonic solutions activated I(Cl, vol) on top of I(Cl, Ca), suggesting that I(Cl, Ca) and I(Cl, vol) are different channels. We conclude that CPAE cells do not express voltage-gated (ClC-type) or cAMP-gated (CFTR-type) Cl- channels, but activate large Cl- currents after volume (mechanical?) or chemical (Ca2+) stimulation.     

1-(8-氨基喹啉-5-偶氮)-8-羟基-3,6-萘二磺酸与铜的显色反应研究

研究了新显色剂 1 (8 氨基喹啉 5 偶氮 ) 8 羟基 3 ,6 萘二磺酸 (简称AQAHNA)与铜 (Ⅱ )的显色反应条件。在Tween 80存在下 ,pH5 0的乙酸 乙酸钠缓冲溶液中 ,AQAHNA与铜形成 2∶1的红紫色络合物 ,其最大的吸收峰位于5 90nm ,表观摩尔吸光系数 (ε)为 8 7× 10 4 。铜浓度在 0～ 0 4mg/L范围内遵守比尔定律。该方法用于铝合金中铜的测定 ,结果满意。     

Sensory modulation of the medial preoptic area neuronal activity by dorsal penile nerve stimulation in rats

The study was aimed at finding out the influence exerted by the genital afferents on the medial preoptic area (mPOA), which plays a pivotal role in the regulation of male sex behavior. To fulfil this objective, the effects of stimulation of the dorsal penile nerve (DPN) on the activity of 82 mPOA neurons were studied. The base line firing rates of the mPOA neurons, studied by extracellular recording, ranged between 0.5 and 38.5 Hz (mean 7.18 +/- 7.91). The stimulation of the DPN (20 Hz, 0.4 msec. 70 microA) influenced 79.69% of the neurons studied. Though increased firing was the predominant influence produced (50%), decreased firing was also seen in a few (29.69%). The excited and inhibited neurons were randomly distributed within the mPOA. Neurons located in the lateral and posterior hypothalamus were not affected by the DPN stimulation. The stimulation parameters used in this study did not produce any change in the systemic arterial pressure and heart rate. The results provide electrophysiological evidence of afferent inputs from the male sex organ to the mPOA, which is an important area controlling male sex behavior.