摘要:

AbstractAlthough bradykinin has been long studied, its biological relevance is still unclear. The enzymes that form and degrade bradykinin appear to be numerous and ubiquitous, and its “receptors” are both species and tissue specific. Therefore, despite the fact that a multitude of compounds have been synthesized and screened as receptor antagonists, to date only one specific antagonist has been identified and it is only active in the rabbit aorta. This review is designed to present what is known about bradykinin receptors in intestinal smooth muscle. Relevant background material and a discussion of evidence for bradykinin's mechanism of action are also presen

ISSN:0272-4391    

DOI:10.1002/ddr.430020102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe increase in the rat striatal concentration of 5‐hydroxyindoleacetic acid (5‐HIAA) elicited by baclofen was antagonized by the 5‐HT antagonists pipamperone (10/30 mg/kg i.p.), cyproheptadine (30 mg/kg i.p.), methiothepin (1 mg/kg i.p.), and GP 50 302 (1/3 mg/kg i.p.), but not by cinanserin (1–30 mg/kg i.p.), pizotifen (1–10 mg/kg i.p.), spiroperdol (0.1–1 mg/kg i.p.), or haloperidol (0.1–1 mg/kg i.p.). The 5‐HT agonists, m‐chlorophenylpiperazine (1 mg/kg i.p.) and MK 212 (3/10 mg/kg i.p.) also showed an antagonistic effect. Methysergide (5–20 mg/kg i.p.) and quipazine (2.5/5 mg/kg i.p.) were previously shown to act similarly, whereas mianserin (5–20 mg/kg i.p.) was inactive and methergoline at lower doses (0.25–0.5 mg/kg i.p.) increased the effect of baclofen, which was reversed at higher doses (1 mg/kg i.p.). The alterations by these compounds of the 5‐HT increase elicited by baclofen were more or less similar; however, they were less clear‐cut and occurred at higher doses. These interactions were not the result of interferences of the compounds with the absorption, distribution, or metabolism of baclofen nor with its effect on the nigrostriatal dopaminergic system, since the increase in dopamine concentrations it caused was not affected by any of the compounds. A comparison of our results with published data on the antagonism of 5‐hydroxytryptophan‐induced head twitches, on spiroperidol or 5‐HT displacement, on 5‐HT‐stimulated adenylate cyclase, and with electrophysiological results suggests that the antagonistic effect of compounds interfering with the 5‐HIAA elevating action of baclofen is not related to 5‐HT receptor blocking properties of these drugs, Instead, it seems to be much more related to 5‐HT agonists properties. It is speculated that this model might reveal presynaptic agonistic properties of drugs, but mor

ISSN:0272-4391    

DOI:10.1002/ddr.430020103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractAnalgesics of various classes, endorphins, and other psychotropic drugs were evaluated for activity in inhibiting3H‐serotonin binding to a soluble serotonin binding protein (SBP) isolated from rat brain. Morphine, leu‐endorphin, and the narcotic antagonist, nalorphine, effectively inhibited binding, while other analgesics, including codeine, methadone, pentazocine, beta‐endorphin, and enkephalins were inactive. Amitriptyline partially inhibited binding, while stimulants did not. Inhibition of serotonin binding to SBP does not appear to be characteristic of narcotic analgescis or any one therapeutic class of comp

ISSN:0272-4391    

DOI:10.1002/ddr.430020104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe analgesic effect of morphine in a mouse writhing assay was enhanced by the simultaneous administration of fluoxetine, an inhibitor of serotonin uptake. Fluoxetine reduced the ED50for morphine and extended the duration of morphine analgesia. The potentiation of morphine analgesia was particularly striking in mice made tolerant by repeated morphine injections. Potentiation of morphine by fluoxetine was also observed in a rat tail jerk test for analgesia. The acute lethality of morphine in rats and mice was altered by fluoxetine, yet the therapeutic index of morphine (ratio of LD50to ED50) was unchanged. The decrease in blood pO2produced by morphine at doses of 1 and 4 mg/kg in rats was attenuated by fluoxetine, which by itself increased blood pO2. These findings strengthen earlier evidence for an involvement of serotoninergic neurons in the analgesic effects of morphine and support the idea that enhanced serotoninergic function might be a useful means of enhancing morphine's actions in clinical therapy.

ISSN:0272-4391    

DOI:10.1002/ddr.430020105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractBoth learned helplessness and stress produce deficits in escape/avoidance behavior. The yoked control paradigm was used to compare these two phenomena, with pairs of animals exposed to the same amount of shock—in one case controllable (stress) and in the other uncontrollable (learned helplessness). Stressed animals demonstrated a transient (one day) elevation in serotonin levels in the septal synaptosomal pellet. On the other hand, animals subjected to uncontrollable footshock sustained a significant decrease in septal synaptosomal serotonin for five days. Similar differences were found in the anterior cortex, but not in the posterior cortex or hippocampus. This work demonstrates the importance of using appropriate controls in neurochemical and pharmacologic research with learned helplessnes

ISSN:0272-4391    

DOI:10.1002/ddr.430020106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractOn the basis of current information about the structure‐activity relationships of anticonvulsant compounds, it is predicted that diphenylacetylurea should possess some degree of antielectroshock activity. However, past attempts to demonstrate this have failed. In the present investigation the authors have determined that this compound does in fact possess such efficacy, although its potency is relatively low in comparison with phenytoin and phenobarbital. The difference in potency among these drugs is greatest when expressed in terms of the i.p. dosage, and much smaller when expressed in terms of blood or brain concentrations. The difference on the basis of i.p. dosage might be due to differences in bioavailability, but the lower potency of diphenylacetylurea expressed in terms of brain concentration is possibly due to its very high lipid solubility, as discussed in the tex

ISSN:0272-4391    

DOI:10.1002/ddr.430020107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractIsoxsuprine has been used in obstetrics in the treatment of premature labor. Its maternal and fetal effects were studied in five ewes with dated gestations of 137 ± 1.25 days (term approximately 147 days).Isoxsuprine (1 mg/min) was infused over a 30‐minute period to the anesthetized ewes while maternal and fetal blood pressures, uterine and fetal cerebral blood flows, and fetal brain function were studied. In addition, fetal and maternal acid‐base values and fetal cerebral metabolism were measured at baseline, 10, 20, 30, 45, and 60 minutes.Isoxsuprine caused maternal hypotension, tachycardia, and metabolic acidosis and temporary reduction of PO2without affecting oxygen saturation, O2content, or uterine blood flow. In the fetus hypotension, tachycardia, temporary metabolic acidosis, transient reduction in PO2and O2saturation occurred while PCO2, cerebral blood flow, brain glucose consumption, and the electroencephalogram remained essentially unchanged. Fetal pH, PO2, and O2saturation returned toward baseline values at the end of the experi

ISSN:0272-4391    

DOI:10.1002/ddr.430020108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractIn an attempt to correlate the behavioral and neurochemical effects of d‐ and l‐amphetamines, the time courses of the effects of the two isomers (1 mg/kg; base, i.p.) were studied on spontaneous motor activity (SMA) and stereotyped behavior (ST) as well as on the concentrations of norepinephrine (NE), dopamine (DA), and serotonin (5‐HT) in discrete brain areas, such as the caudate nucleus (CN), pons‐medulla (PM), and diencephalonmidbrain (DM) in rats. In addition, the dose‐response relationship for d‐isomer (0.5–2 mg/kg, i.p.) and l‐isomer (1–4 mg/kg, i.p.) was also studied on SMA and ST. SMA increased with the dose up to 1.5 mg/kg for d‐isomer and up to 3 mg/kg for l‐isomer and then decreased, whereas ST increased with the dose for both the isomers. At 1 mg/kg dose, SMA reached its peak during the fourth postdrug 20–minute period for both d‐ and l‐isomers, whereas ST reached its peak during third to fifth 20‐minute periods for d‐isomer and during the third period for the l‐isomer. The d‐isomer significantly increased the DA levels in the CN and DM at 30 minutes postdrug, which reached their maximum at 60 minutes, whereas NE levels in the PM had no significant change at 30 minutes, but were significantly reduced in the DM at 30 minutes and in both PM and DM at 60 minutes postdrug; 5‐HT levels in the PM and DM showed no significant change. Compared to d‐amphetamine, the l‐isomer at 30 and 60 minutes postdrug caused more or less similar changes in the NE levels in the DM and PM, whereas it produced less increase in the DA levels in the CN and DM and significant decrease in 5‐HT levels in the DM and PM. It appears that the difference in the behavioral effects induced by the two isomers of amphetamine may be due to the difference in their effec

ISSN:0272-4391    

DOI:10.1002/ddr.430020109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractFemale rats, anaesthetized with hexobarbital, regained their righting reflex more rapidly following electrostimulation than sham‐treated controls. The extent of the decreased sleeping times in these animals varied according to the frequency (cycles per second) of the electrostimulation applied. The frequency which produced the largest decrease in sleeping time was 10 Hz. Determination of the activity of some microsomal enzymes indicated that the decreased sleeping time was not the result of increased hepatic enzyme activity. Animals which had received prior treatment with naloxone exhibited increased sleeping times following barbiturate administration, but the effects of electrostimulation on the sleeping time at 10 Hz was diminished, while the effect of electrostimulation at high frequency (500 Hz) was enhanced. Although repeated daily administration of hexobarbital progressively decreased sleeping times for all the animals, electrostimulation decreased the sleeping times of the treated rats by a similar percentage of the control animals on each successive day. Electrostimulation at a frequency of 10 Hz produced a significant decrease in serum corticosterone levels, whereas 500 Hz resulted in an increas

ISSN:0272-4391    

DOI:10.1002/ddr.430020110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractUsing several different experimental conditions, centrifugation assays revealed that no “specific” high‐affinity Na+‐independent binding of [3H]GABA (3–15 nM) or [3H]muscimol (6–92 nM) occurred to subcellular particles prepared from C6glioma cells. Therefore, like the membranes of glial cells grown in primary culture and like the modified oligodendroglial membranes of myelin, the transformed glial membranes of C6cells do not appear to possess GABA‐receptors. These results provide further evidence that the depolarizing actions of GABA on glia that have been recorded in electrophysiological studies occur indirectly rather than by activation of glial G

ISSN:0272-4391    

DOI:10.1002/ddr.430020111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY