Brain injury following cardiorespiratory arrest in cats. Effects of alphaxalone-alphadolone

The effects of alphaxalone-alphadolone acetate (27.07 microM/kg-7.68 microM/kg) on neurologic injury following acute cerebral ischemia induced by an 8 min cardiorespiratory arrest (CRA) were investigated in cats through the analysis of neurological deficit scores and brain electrical activity; i.e., electroencephalogram (EEG) from parieto-occipital cortices and EEG and multiunit activity (MUA) from mesencephalic reticular formation (MRF). The CRA resulted from electrically induced cardiac arrest and stopping of mechanical ventilation in paralyzed cats which were successfully resuscitated within the immediate 4 min after the end of CRA. Two groups of cats were studied: I. Untreated, which received saline iv; II. Treated, which received alphaxalone-alphadolone acetate iv, 7-9 min after the end of CRA. Neuromuscular blockade and mechanical ventilation were maintained until 8 h following the CRA; then the cats were allowed to recover spontaneous respiratory activity. EEG phenomena were different in untreated and treated cats during this immediate post-arrest period. The former showed rhythmic bursts of fast (12-20 Hz) EEG activity at 1-2 sec intervals from 15-20 min until 3-4 h after the CRA, abundant spikes and delta-like waves. By contrast, administration of alphaxalone-alphadolone acetate resulted in burst suppression EEG pattern during 1 h. Progressive recovery of background EEG activity occurred afterwards. MUA from MRF disappeared during the CRA, however 6 h later the mean MUA frequency in untreated cats ranged between 32-46% and in treated cats 18-27% of their control mean frequencies during paradoxical sleep (100%). Daily electrographic records were performed in all the cats during quiet attentive behavior at each of the five days following the CRA. Significant differences were found in the frequency distributions of MUA from MRF (1st day, p less than 0.01; 5th day, p less than 0.01) as well as in the cortical EEG waves (1st day, p less than 0.01; 5th day, p less than 0.05) before and after the CRA in the untreated group. A wide dispersion of MUA values, and increased proportions of delta and theta-like waves and spindle bursts, besides a significantly high (p less than 0.001) number of spikes occurred in these EEG records the days following the CRA. The frequency distributions of MUA and EEG did not significantly differ before and after the CRA in the treated group; however, a significantly high (p less than 0.05) number of spikes was found in treated cats following the CRA.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modifications of acoustic habituation by interruption of visual input in quipazine treated cats

The influence of interruption of the visual input on acoustic habituation was studied in cats before and following the administration of quipazine, 3 mg/kg iv. The characteristics of acoustic habituation were analyzed through the magnitude and temporal course of multiunit activity (MUA) responses elicited in the mesencephalic reticular formation (MRF) by repetitive acoustic stimuli (70 db, 50 Hz trains of 2 sec duration) in 6 freely moving cats with cortical electrodes over the parietal cortex and bipolar electrodes chronically implanted in MRF and basolateral amygdala (AMN). The cats were submitted to repetitive acoustic stimulation during one 30 min period before, and three 30 min periods after drug administration in the following conditions: a) with unmasked eyes; b) with masked eyes by means of dark contact lenses. Persistent attentive behavior, catatonic attitudes, hypersynchronous (6 Hz, 100-150 microV) EEG activity and significant increase of spontaneous MUA in FRM and AMN were induced by quipazine both in the cats tested with unmasked and with masked eyes. This increase of MUA was higher immediately following drug administration and progressively decreased, although MUA values remained significantly higher than controls 110 min after quipazine administration. Acoustic habituation, evidenced through the progressive decrease of MUA responses of MRF to acoustic stimuli, was observed before quipazine administration when the cats were tested with unmasked and with masked eyes; as well as in cats tested with unmasked eyes following drug administration. However, the MUA responses to acoustic stimuli did not decrease in cats with masked eyes during acoustic stimulation periods 0-30 min and 40-70 min after quipazine administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of spreading depression on stress-induced changes in plasma prolactin and LH.

Female rats rendered "pseudopregnant" by treatment with PMS and hCG and ovariectomized rats injected with estradiol and progesterone (OVX-E2-P) were subjected to cortical spreading depression (SD). Within 7-10 min under ether anesthesia in a stereotaxic instrument a frontal craniotomy was performed and a cotton ball saturated with physiological saline (control) or 25% KCl was applied to the exposed dura, covered with dental cement and skin sutured. The animals were then placed in separate containers in an isolated room and decapitated for collection of trunk blood at 0, 15, 30, or 60 min after surgery. In PMS-hCH saline-treated control animals, prolactin levels had dropped by 15 and 30 min when compared with the zero-time values but by 60 min had increased significantly above the 30-min level. At that time (60 min), prolactin values in the KCl group were significantly lower than in the controls. Corticosterone levels were high at both 15 and 60 min in control and KCl groups. In OVX-E2-P control animals, plasma prolactin levels also rose at 60 min compared with 15- and 30-min samples and at 60 min were significantly higher than in the KCl group. In control animals, LH levels were lower at 15 and 60 min than at zero time, but they remained unchanged in the KCl group. The dato are interpreted as indicating that cortical SD suppresses the stress responses observed in saline-treated control animals.     

Changes in the phasic activity of neuron microsystems of the somatosensory cortex of the cat during extinction of activation reactions to unreinforced stimuli

In chronic experiments on cats, three-phasic responses of neuronal microsystems in the cortical somatic area I were studied during habituation of the EEG activation reactions. Repeated stimuli of different modalities were used: electrical pulses to the forepaw, sounds, direct stimulation of the mesencephalic RF. Simultaneously with the extinction of EEG activation reactions, the three-phasic responses of the multiunit activity (MUA) also became progressively extinct: the 1st phase of primary excitation--only a little, the 2nd phase (inhibitory)--greatly, as well as the 3rd phase--the phase of secondary excitation (if it existed at the beginning). The MUA responses to all stimuli show that these neuronal microsystems are polysensory. Relatively to the nonspecific activating RF macrosystem, the investigated neuronal microsystems are autonomous because their two functionally opposed response phases--the 1st excitatory and the 2nd inhibitory--occur against the monotonous excitatory background of the EEG activation. But in some way the neuronal microsystems are connected with the RF-system because of the parallel development of the extinction process.     

Response of the hypothalamo-corticotropic system to metyrapone in pigeons

Chronic catheterization and miniature recording device allowed plasma corticosterone (B) and hypothalamic multiunit activity (MUA) to be simultaneously obtained from freely behaving, awake pigeons, before and for 4 hrs after intravenous injection of metyrapone. Injection of vehicle (tartric acid : 100 mg/4 ml/kg) led to MUA and B profiles quite similar to stress-induced responses, i.e., a rapid and sustained rebounding increase in hypothalamic firing rate and, shifted by 5-10 min, in plasma B. These responses were progressively attenuating for 90-120 mn. Metyrapone administration induced first a rapid and short MUA and B increase. Then both parameters drastically decreased near zero for about 2 hrs and were slowly restored to initial values within 3-4 hrs. It is suggested that metyrapone treatment inhibited both peripheral (B synthesis) and central (hypothalamic neurons) levels of the corticotropic axis.     

Effects of nimodipine on multiunit activity of several brain structures following acute global cerebral ischemia-anoxia in cats.

The effects of nimodipine, a 1,4-dihydropyridine calcium channel blocker, on multiunit activity (MUA) of several brain structures were investigated in cats during 6 h immediately following acute global cerebral ischemia-anoxia induced by a 10 min cardiorespiratory arrest (CRA), as well as in cats exposed to sham procedures corresponding to CRA. Four groups of cats were studied: 1) CRA and continuous administration of nimodipine, 1 microgram/kg/min iv during 6 h; 2) CRA and continuous administration of vehicle; 3) sham and continuous administration of nimodipine as in group 1; 4) sham and vehicle as in group 2. MUA and electroencephalogram disappeared during ischemia-anoxia; their progressive recovery occurred throughout the hours following CRA, although 6 h after CRA MUA was still lower than its control prearrest values in all the recorded subcortical structures. Delta-like waves, isolated spikes, and bursts of fast EEG waves occurred during the recovery of EEG activity. Nimodipine inhibited the otherwise increasing MUA in mesencephalic reticular formation, hippocampus and putamen, but not in ventromedial hypothalamus, during the hours following acute global cerebral ischemia-anoxia. Absence of isolated spikes and bursts of fast EEG activity was noted in the EEG of CRA-, nimodipine-treated cats. Nimodipine significantly reduced MUA in hippocampus but not in other cerebral structures in cats of the sham treated group. The results suggest the involvement of 1,4 dihydropyridine sensitive calcium channels in the cellular mechanisms related to neuronal activity after cerebral ischemia-anoxia, and the possible relationship between the effects of nimodipine on MUA and better functional conditions of the central nervous system after acute global cerebral ischemia-anoxia.     

大鼠脑室内注射ANGⅡ和ANGⅡ抗体对尿钠排出和肾皮质...

In anesthetized rats, it was observed that intracerebroventricular (I.C.V.) microinjection of angiotensin II (ANG II) in a dose of 16 pg evoked a significant increase in renal sodium excretion which began within 15 min and lasted for 90 min. The activity of Na+.K(+)-ATPase in renal cortex after I.C.V. microinjection of ANG II (1.51 +/- 0.26 mumol Pi/mg Pro.h) was inhibited as compared with that of the control injecting of artificial cerebrospinal fluid (2.66 +/- 0.28 mumol Pi/mg Pro.h, P less than 0.01). There was no change in mean arterial pressure. Within 15 min after I.C.V. administration of ANG II antibody, however, and antinatriuretic period of 135 min and a higher activity of Na+.K(+)-ATPase in renal cortex (3.61 +/- 0.34 mumol Pi/mg Pro.h, P less than 0.05 compared with control) were observed. There was no natriuresis in the animals microinjected with ANG II either into femoral vein or into spinal subarachnoid space. The result of the present investigation suggests that brain endogenous ANG II may possess some natriuretic activity possibly through inhibiting renal Na+.K(+)-ATPase activity.     

Analysis of farnesyl transferase activity during hormone-induced maturation of Xenopus laevis oocytes

Preincubation of Xenopus laevis oocytes with insulin or insulin-like growth factor 1 (IGF-1) resulted in inhibition of farnesyl transferase (FTase) activity measured both in vivo (after microinjection of tritiated farnesyl pyrophosphate and Ras-CVIM into oocytes) and in extracts using a filtration assay. FTase activity measured in oocyte extracts was inhibited 55% after a 20 min treatment of oocytes with 1 microM insulin or 10 nM IGF-1. The apparent IC(50) for inhibition of oocyte FTase by IGF-1 is 0.3 nM. The observed decrease in FTase activity was apparently not due to translocation of enzyme from cytosol to membrane, since activities measured both in soluble extracts and resuspended crude pellets displayed comparable levels of inhibition following hormone treatment. Using a hexapeptide (TKCVIM) as substrate, FTase activity was also inhibited 65% when oocytes were pretreated with 10 nM IGF-1. Two FTase inhibitors [(alpha-hydroxyfarnesyl) phosphonic acid (HFPA) and chaetomellic acid A (CA)] effectively inhibited Xenopus oocyte FTase by 80-90% when added to assay mixtures (IC(50) values of 338 +/- 96 nM HFPA and 232 +/- 80 nM CA) or after incubation of oocytes in drug before preparation of soluble extracts for assay (IC(50) values of 7 +/- 6 nM HFPA and 328 +/- 128 nM CA). The farnesyl transferase inhibitors were observed to slow the time course of oocyte maturation but did not block the IGF-1-induced maturation response. J. Exp. Zool. 286:193-203, 2000.Copyright 2000 Wiley-Liss, Inc.     

The effect of neomycin on contractile activity of the canine cervical lymphatic vessel induced by various agents

The effects of neomycin on isometric contractions induced by norepinephrine (NE), alpha 1-adrenoceptor agonist phenylephrine (PE), KCl, and an activator of GTP-binding proteins (G-proteins) NaF were studied in the isolated canine cervical lymphatic vessel (CLV). Incubation of the CLV with 0.3 or 1.3 mmol/l neomycin for 30-180 min did not affect significantly either the basal vascular tone or the response to NE, and potentiated the response to KCl by 24 +/- 6% (p less than 0.05). On the other hand, neomycin (1.3 mmol/l) treatment reduced by 22 +/- 6% (p less than 0.05) the contractions induced by PE and completely (by 96 +/- 3%, p less than 0.001) suppressed the effects of NaF. Upon the combined action of NaF and NE, neomycin reduced only NaF-component of the total response. Verapamil (100 mumol/l) had no effect on the magnitude of NaF-induced tension and partially inhibited NE- and PE-induced contractions (by 20 +/- 4% (p less than 0.05) and 53 +/- 5% (p less than 0.01), respectively). Indomethacin (10 mumol/l) did not influence significantly the contractions evoked by NE, KCl, and NaF either under control conditions or in the presence of neomycin. These data suggest that the phosphoinositides may considerably contribute to the CLV contractions evoked by NaF, but do not play a substantial role in the responses of the vessel to alpha-adrenergic stimulation and KCl.     

Monitoring of potassium-stimulated catecholamine changes in striatal synaptosomal preparations and in corpus striatum of rats: a comparative voltammetric study.

Voltammetric techniques were used to compare the effects of K(+)-induced depolarization on catecholamine levels in in vitro synaptosomal preparations of the corpus striatum with those in the in vivo corpus striatum of anaesthetized animals. In vitro, the catechol-oxidation currents could be recorded only in dopamine-preloaded synaptosomes. In isolated synaptosomes prepared in the presence of elevated concentrations of Ca2+ (1 mmol.l-1) and Na+ (135 mmol.l-1), K(+)-induced depolarization had variable effects on catechol-oxidation current. The stimulatory effect of K(+)-induced depolarization (a short transient increase of catechol-oxidation current lasting for 30 s) could be observed after the addition of dopamine loaded synaptosomes in EGTA into the medium with elevated K+ concentration (90 mmol.l-1) and decreased concentrations of Na+ (75 mmol.l-1) and Ca2+ (0.75 mmol.l-1). These results suggest that experimental procedures and parameters of ionic composition of incubation media have to be carefully controlled, owing to an enhanced in vitro permeability of membranes of isolated synaptosomes for Ca2+ and Na+. In in vivo experiments, microinjection of KCl (3 microliters of 0.5 mol.l-1 KCl in 10 mmol.l-1 HEPES, pH 7.4) resulted in the appearance of several phases of catechol-oxidation current: the current increased (to severalfold of the control values) followed by a decrease or even total disappearance, with a gradual return to control values. Under conditions of depletion of extracellular calcium by EGTA (5 microliters of 0.5 mol.l-1 KCl + 0.25 mol.l-1 EGTA in 10 mmol.l-1 HEPES, pH 7.4) K(+)-induced depolarization confirmed the key role of calcium in the release of catecholamine transmitters as well as that in processes regulating the uptake and metabolism of these transmitters. The voltammetric techniques used in the present study may be a useful tool in extending of our knowledge about the cellular mechanisms of stimulus-response coupling in nerve cells.     

大鼠神经源性肺水肿时交感神经放电活动,血浆儿...

Neurogenic pulmonary edema (NPE) was induced by microinjection of kainic acid into bilateral preoptic area (POA) of the hypothalamus in rats. Sympathetic discharge of the left adrenal branch was recorded, plasma catecholamine (CA) was assayed and the physical properties of pulmonary surfactant (PS) of the lung lavage were measured. The results showed that some physical properties of PS were changed in NPE, i.e. maximal surface tension (gamma Max) decreased, minimum surface tension (gamma Min) increased, recruitment index (RI), stability index and area of hysteresis loop (H-area) decreased. After injection of kainic acid into POA, the sympathetic discharge increased by 22.8 +/- 7.20% and 32.2 +/- 8.0% respectively at 30 and 60 min after injection and paralleled by a marked elevation of plasma catecholamine (CA). The results showed that PS activity had decreased at an early stage of NPE and the change of the plasma CA level was parallel to that of sympathetic discharge. It is suggested that generation of NPE may be related to some disorder of the autonomic nervous system at the level of hypothalamus, increase of sympathetic discharge, elevation of plasma CA level and fall of PS activity.     

Biodegradation of the sulfonylurea herbicide chlorimuron-ethyl by the strain Pseudomonas sp. LW3

Eleven carbazole (CAR)-degrading bacterial strains were isolated from seawater collected off the coast of Japan using two different media. Seven isolates were shown to be most closely related to the genera Erythrobacter, Hyphomonas, Sphingosinicella, Caulobacter , and Lysobacter . Meanwhile, strains OC3, OC6S, OC9, and OC11S showed low similarity to known bacteria, the closest relative being Kordiimonas gwangyangensis GW14-5 (90% similarity). Southern hybridization analysis revealed that only five isolates carried car genes similar to those reported in Pseudomonas resinovorans CA10 ( car _CA10) or Sphingomonas sp. strain KA1 ( car _KA1). The isolates were subjected to GC-MS and the results indicated that these strains degrade CAR to anthranilic acid.     

Changes induced by 6-hydroxydopamine in the paraventricular nucleus

Summary Remodelling of catecholaminergic (CA) fibers after cerebral intraventricular 6-hydroxydopamine (6-OH-DA) administration was evaluated quantitatively in the paraventricular nucleus (PAR) of young adult rats, using fluorescence microscopy (FM) and electron microscopy (EM). Fluorescent CA varicosities and CA boutons (marked with 5-OH-DA) were counted after survival periods of 4, 21, 56 or 180 days. Four days after 6-OH-DA treatment, the number of fluorescent varicosities dropped to 45% of control numbers but was restored to 79% of control values by 180 days. In the EM study, marked boutons had dropped more dramatically: to 12% of control numbers, after 4 days and 54% by 180 days post-neurotoxin. These data provide strong evidence that substantial but incomplete restoration of CA terminals occurred in PAR. It is of interest that, in all survival intervals, percentage reductions in numbers of CA terminals were more extreme when EM was used for quantification. Nevertheless, the trends indicating partial restoration of terminal numbers with time were parallel in the FM and EM studies. Structures identified as CA growth cones in PAR contained a feltwork of fine filaments together with mitochondria, granular vesicles (often with electron-dense cores marked by the 5-OH-DA label), vacuoles and smooth-surfaced reticulum. The presence of growth cones, some of which persisted 11 months after neurotoxin administration, further supports the inference that a regenerative response of CA elements was evoked in PAR by the 6-OH-DA treatment.Presented in part at IV International Catecholamine Symposium in California, September 1978     

Mobile telephone use effects on peripheral audiovestibular function: a case-control study

Low level radio-frequency (RF) signals may produce disorientation, headache and nausea. This double blind study tested nine case-subjects, who complained of various symptoms after prolonged mobile telephone use and 21 control subjects. Each subject underwent a series of trials, in which a dummy mobile telephone exposure system was held to each ear for 30 min in (a) pulsed, (b) continuous RF emission or, (c) no emission test modes. In the active pulsed and continuous modes the same mean power as the output of a typical handset was delivered at a carrier frequency of 882 MHz and at a maximum specific absorption rate (SAR) value of 1.3 W kg(-1) (+/- 30%). In Experiment I (auditory), transient evoked otoacoustic emissions (TEOAE), which assess the outer hair cells in the inner ear, were conducted. In Experiment II (vestibular) the vestibulo-ocular reflex was recorded by video-oculography (VOG), at baseline and immediately post exposure. There were no significant TEOAE changes from baseline to post-exposure recording for any of the exposures and no significant differences in the TEOAEs' change from baseline to post exposure between cases and controls. The VOG did not identify any effect of the exposure on the vestibular end organ in either cases or controls. In conclusion, 30 min exposure to mobile phone RF did not show any immediate effects on vestibulocochlear function as measured by TEOAE and the VOR.     

Anoxia reversibly suppresses neuronal calcium currents in rat hippocampal slices

Intracellular recording from CA1 neurons confirmed that short periods of anoxia (95% N2 + 5% CO2 for 2-4 min) have a hyperpolarizing action, caused by a rise in K conductance. After blockage of K channels with extracellular Cs+ and tetraethylammonium (or intracellular Cs+), large inward currents of Ca were evoked by depolarizing pulses: transient currents at a holding potential near -70 mV, and more sustained ones near -50 mV. Both types of Ca current were much reduced or fully suppressed after 1-3 min of anoxia, but they largely (or fully) recovered within 1-10 min of starting reoxygenation.     

Evidence for biorhythmicity from the preoptic nucleus of the rainbow trout Salmo gairdnerii under freely swimming conditions--an electrophysiological study

This study describes a technique which allows continuous recording of MUA (Multiple Unit Activity), from the NPO (Preoptic Nucleus), DAP (Dorsal Aortic blood Pressure) and ECG (Electrocardiogram) in freely swimming rainbow trout. From the 21 trout tested, six trout (29%) clearly showed rhythmic patterns of MUA during the five post-operative days (D2-D6). The mean length of rhythmic MUA was about 18 hr (range 6-33 hr) among the six trout during the recording days. Periodic MUA occurred approximately eight times/hr and lasted about 2 min. The maximal frequency of discharges was 20-30 spikes per sec. No change occurred in the mean level of blood pressure from the first operative day to the following post-operative days, where rhythmic MUA appeared or reappeared. These results demonstrate the existence of biorhythmicity within the NPO of freely swimming trout and suggest parallel oscillations in neurohormones secretion.     

Involvement of Rho/Rho-kinase signalling in the contractile activity and acetylcholine release in the mouse gastric fundus

In this study effects of Rho kinase inhibitors have been examined on the mouse gastric fundal smooth muscle reactivity and neurotransmitter (acetylcholine) release. Two Rho-kinase inhibitors, Y-27632 and fasudil (HA-1077), conspicuously suppressed the contractile responses to carbachol (CCh) and KCl as well as electrical field stimulation (EFS, 40 V, 0.5 ms, and 20 s). pEC(50) value for CCh and EC(50) value for KCl were 6.68+/-0.15 M and 10.4+/-2.8 mM, respectively. EFS induced reproducible contraction (38.3+/-4.75 mN/g tissue) which was almost abolished and potentiated in the presence of atropine (10(-6)M) and eserine (10(-6)M), respectively. The Rho-kinase inhibitors relaxed the fundic strips preconstricted by submaximal concentration of CCh or KCl in a concentration dependent manner. With CCh-elicited contraction, the pEC(50) values of Y-27632 and fasudil were 5.45+/-0.14 and 5.11+/-0.14 M, respectively (p>0.05). However, the pEC(50) values for Y-27632 and fasudil on KCl-induced tone were 6.09+/-0.1 and 5.35+/-0.06 M (p<0.001), respectively. Moreover, [3H]acetylcholine ([3H]ACh) release upon EFS from the gastric fundus was measured and it was found that Y-27632 (10(-4)M) significantly impaired the release. At 3 Hz the radioactivity ratio obtained after and before EFS (S(2)/S(1) ratio) was 0.88+/-0.03 in control but 0.63+/-0.08 in the presence of 10(-4)M Y-27632 (p<0.05). These results suggest that Rho kinase inhibitors can not only relax the gastric fundus but also modulate CCh, cholinergic nerve stimulation, and KCl-induced contraction. Furthermore, Rho/Rho kinase signalling may play a role in the neurotransmitter (ACh) release in the mouse gastric fundus.     

[14C]Leucine Incorporation into Brain Proteins in Gerbils After Transient Ischemia: Relationship to Selective Vulnerability of Hippocampus

Regional [14C]leucine incorporation into brain proteins was studied in gerbils after global ischemia for 5 min and recirculation times of 45 min to 7 days, using a combination of quantitative autoradiography and biochemical analysis. After recirculation for 45 min, incorporated radioactivity was reduced to approximately 20-40% of control values in all ischemic brain regions. Specific activity of the tracer, in contrast, was increased, a finding indicating that the reduced incorporation of radioactivity was not due to reduced tracer influx from plasma or a dilution of the tracer by increased proteolysis. After recirculation for 6 h, [14C]leucine incorporation returned to control levels in all regions except the CA1 sector of the hippocampus, where it amounted to less than 50%. After 1 day, protein synthesis in the CA1 sector returned to approximately 70% of control values, followed by a secondary decline to less than 50% after 3 days and returned to near control values after 7 days. Histological evaluations revealed selective neuronal death in the CA1 sector of the hippocampus after 3 days of recirculation. The complex time course of protein synthesis in the CA1 sector suggests a biphasic mode of injury, which may be related to similar changes of calcium homeostasis. The final return to near normal after CA1 neurons have disappeared is explained by astroglial proliferation and demonstrates that at this time protein synthesis is not a marker of neuronal viability.     

Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue

We determined whether the dorsomedial hypothalamus (DMH) plays a role in the thermogenic, metabolic, and cardiovascular effects evoked by centrally administered PGE2. Microinjection of PGE2 (170 pmol/60 nl) into the medial preoptic area of the hypothalamus in urethane-chloralose-anesthetized, artificially ventilated rats increased brown adipose tissue (BAT) sympathetic nerve activity (SNA; +207 +/- 18% of control), BAT temperature (1.5 +/- 0.2 degrees C), expired CO2 (0.9 +/- 0.1%), heart rate (HR; 106 +/- 12 beats/min), and mean arterial pressure (22 +/- 4 mmHg). Within 5 min of subsequent bilateral microinjections of the GABAA receptor agonist muscimol (120 pmol.60 nl-1.side-1) or the ionotropic excitatory amino acid antagonist kynurenate (6 nmol.60 nl-1.side-1) into the DMH, the PGE2-evoked increases were, respectively, attenuated by 91 +/- 3% and 108 +/- 7% for BAT SNA, by 73 +/- 12% and 102 +/- 28% for BAT temperature, by 100 +/- 4% and 125 +/- 21% for expired CO2, by 72 +/- 11% and 70 +/- 16% for HR, and by 84 +/- 19% and 113 +/- 16% for mean arterial pressure. Microinjections outside the DMH within the dorsal hypothalamic area adjacent to the mamillothalamic tracts or within the ventromedial hypothalamus were less effective for attenuating the PGE2-evoked thermogenic, metabolic, and cardiovascular responses. These results demonstrate that activation of excitatory amino acid receptors within the DMH is necessary for the thermogenic, metabolic, and cardiovascular responses evoked by microinjection of PGE2 into the medial preoptic area.     

Somatostatin pretreatment facilitates GRF-induced GH release and increase in free calcium in pituitary cells

Somatostatin pretreatment sensitizes rat anterior pituitary to hGRF stimulation in vitro. The pretreatment (1 nM for 10 min) facilitated GH release response of dispersed rat anterior pituitary cells to hGRF (1 nM for 3 min) 2.04-fold in a perifusion system. The effect lasted even 20 min after the pretreatment. SRIF pretreatment decreased cAMP content in the cells after hGRF stimulation to 61% of the control value. When hGRF was replaced by 1 mM DBcAMP and 15 mM KCl, the pretreatment increased GH secretion 1.69- and 1.67-fold respectively. SRIF pretreatment (1 nM for 10 min) caused a larger increase in (Ca2+)i by hGRF than that of control. The effect of SRIF pretreatment facilitates GRF-induced increase in GH secretion probably through the stimulation of increase in (Ca2+)i.