Involvement of central histamine receptors in corticosterone secretion induced by intraventricular administration of morphine

The effect of intracerebroventricular (i.c.v.) administration of morphine on corticosterone secretion was studied in conscious, unstressed rats. A dose-dependent increase in serum corticosterone levels was observed 1 h after morphine injection. The corticosterone response to morphine was antagonized in a dose-dependent manner, and at larger dose almost abolished, by i.c.v. pretreatment of rats with naloxone, an opioid receptor antagonist. Intraventricular pretreatment of rats with mepyramine and cimetidine, the histamine H1- and H2-receptor antagonists, significantly diminished the corticosterone response to morphine. These results suggest that central opioid receptors are involved in the stimulating effect of morphine on the hypothalamo-pituitary-adrenocortical axis. Central histamine H1- and H2-receptors seem to be substantially involved in the stimulatory effect of morphine on corticosterone secretion in conscious, unstressed rats.     

Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent

The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 microg/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca(2+), similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187, histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G(i) subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.     

Inhibition by cholinergic agonists of the prolactin release induced by morphine

Summary The cholinergic agonists, pilocarpine, physostigmine and nicotine, inhibited the prolactin release induced by morphine in male rats in vivo. Pilocarpine also inhibited the release of prolactin induced by -endorphin or metoclopramide without affecting the basal and haloperidol-stimulated serum prolactin levels. The inhibitory effect of pilocarpine on the morphine-stimulated release of prolactin was antagonized by concurrent administration of atropine but not by atropine methylnitrate or by mecamylamine, while the inhibition by nicotine was antagonized by mecanylamine but not by atropine. The stimulation of prolactin release by morphine and its reversal by pilocarpine were observed after the administration of haloperidol or -methyltyrosine. These results suggest that the central cholinergic system exerts an inhibitory influence on the prolactin release induced by morphine or -endorphin and the cholinergic inhibition is not mediated via catecholaminergic neurons.     

A novel acute toxicity resulting from the administration of morphine and Adriamycin to mice

The toxic potential of the combination of morphine and Adriamycin (doxorubicin) has been evaluated in mice. Intravenous administration of 20 or 40 mg Adriamycin/kg resulted in a dose-related mortality beginning 4 days postdose. Increasing the dose of Adriamycin to 75 mg/kg caused a biphasic mortality pattern, with 30% of the animals dying within 30 min of drug treatment. Pretreatment with morphine (20 mg/kg) reduced by 80% the dose of Adriamycin required to induce a 30% mortality at 30 min post-Adriamycin administration. Morphine pretreatment also caused a dose-dependent increase in plasma Adriamycin, as measured by total plasma fluorescence. Morphine or Adriamycin administered alone resulted in a slight hematocrit increase. The combination of morphine and Adriamycin caused an increase in hematocrit to maximal levels of approximately 75% from basal levels of about 48%. The increase in hematocrit after morphine plus Adriamycin exceeded the rise caused by higher doses of Adriamycin which, without morphine, resulted in similar plasma Adriamycin levels. The temporal relationship between the elevated hematocrit and early (30 min) mortality suggest a cause/effect relationship between these two events following combined morphine plus Adriamycin treatment.     

Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature.

1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature. 2 Histamine release induced by A23187 in the presence of calcium 10(-3) mol/l was completed in 10 minutes. By preincubation of the mast cells with A23187 for 10 min in the absence of calcium the histamine release induced by calcium, 10(-3) mol/l or 5 x 10(-3) mol/l, was completed in 90 s and 45 s, respectively. 3 A23187-induced histamine release was maximal with calcium 10(-3) mol/l when the cells were incubated at 33 to 39 degrees C for 10 minutes. 4 The cellular mechanism, which was stimulated by A23187 and calcium for the release of histamine, was irreversibly inactivated by incubation at 45 degrees C. 5 An inhibition of energy metabolism was excluded as the cause of the heat inactivation. 6 The dependence of A23187-induced histamine release on calcium and temperature, the time course of histamine release and the heat inactivation are consistent with the view that the same mechanism is involved in A23187-induced and anaphylactic histamine release.     

Lipolytic responses induced by intracerebroventricular administration of histamine in the rat

Histamine (10-50 microgram) administered intraventricularly in conscious rats induced an increase in serum-free fatty acids. The maximum, significant increase appeared 30-60 min after administration. Histamine H1-receptor antagonists, mepyramine and chloropyramine, when injected 2 h prior to histamine, abolished considerably hyperlipaemic responses to histamine. H2-Receptor antagonists, metiamide and cimetidine, given i.c.v. only moderately diminished histamine-induced hyperlipaemia. Histamine injected i.c.v. also increased serum corticosterone levels considerably. This elevation was prevented significantly by the H1-receptor antagonist, mepyramine, but not by the H2-receptor blocker, cimetidine. It seems likely that histamine given i.c.v. induces lipolysis through the release of ACTH, one of the known lipid-mobilizing hormones. The central lipid-mobilizing mechanism after histamine depends more on activation of H1- than H2-receptors.     

Increased fat consumption induced by morphine administration in rats

Patterns of caloric intakes and dietary self-selection of the three macronutrients, protein, fat and carbohydrate were examined in male rats following the administration of morphine sulfate (0.0, 1.0, 10.0 and 20.0 mg/kg, IP). Animals were given access to either ground Purina Chow or one of two dietary self-selection regimes, one with a high-fat ration (7.8 kcal/g) and the other with a fat ration isocaloric to the carbohydrate and protein rations (3.8 kcal/g). Animals received morphine injections at the beginning of a six-hour feeding period and nutrient intakes were measured at 1,2,4 and 6 hours postinjection. Similar patterns of macronutrient choice were observed for both animals maintained on the high-fat regime and animals with access to the isocaloric components following morphine injections. As a function of morphine injections, animals on both self-selection regimes increased fat intake while suppressing carbohydrate intake and exhibiting little modifications in protein intake.     

Dimethyl sulfoxide inhibits histamine release induced by various chemicals

Dimethyl sulfoxide was found to inhibit histamine release induced by compound 48/80 at concentrations ranging from 0.6 to 10%. At higher concentrations (20 and 40%) the substance caused histamine release by itself. Heat inactivation at 50 degrees C of the mast cells did not prevent this release, suggesting a lytic mechanism for this action and this was further proved by the trypan blue dye exclusion test. Dimethyl sulfoxide was also active in inhibiting histamine release induced by other polyamines such as bradykinin, polymyxin B and protamine, by concanavalin A and dextran, by ionophore A23187 and by three anthracyclines, doxorubicin, daunomycin and epirubicin. In contrast, the substance did not inhibit histamine release induced by a monoamine, chlorpromazine and by the detergent Triton X-100.     

The mechanism of histamine release induced by the ionophore X537A from isolated rat mast cells. II. The relationship between increase of cell volume and histamine release.

The ionophore X537A induced swelling of isolated rat mast cells parallel to histamine release. Both actions were depressed by extracellular calcium and BSA, temperatures below 37 degrees C, NEM, PMSF, and TTX, and were enhanced by high potassium and pretreatment of the cells with ATP. DSCG, theophylline, and DFP enhanced the histamine release noted after 10 min of incubation without influencing the swelling action of X537A. The swelling action could not be separated from histamine release and it is suggested that it might be inherent in the mechanism of secretion induced by X537A. The present results further distinguish histamine release induced by the two ionophores X537A and A23187.     

Mast cells and peptide induced histamine release

Mast cells are a heterogeneous population of cells, widely distributed in vertebrates, especially within connective tissues and in areas interfacing the external environment. Mast cells do not circulate as mature cells, it is postulated that mast cell differentiation is not complete until it reaches its target tissue where mast cell phenotype and activity may be modulated by a variety of endogenous and exogenous factors. Mast cell activation may occur via two possible routesimmunological and non-immunological activation. In vitro many physiological compounds, including peptides have been observed to trigger selective mast cell secretion. The mechanism by which peptides induce secretion of inflammatory mediators is unclear. This review concentrates on the main events and signalling pathways of peptide induced mast cell degranulation. Peptidergic activation highlights the multifaceted nature of the mast cell and suggests a pivotal role for the cell in homeostasis.     

Catalepsy, hypermotility, increase of striatal acetylcholine release induced by morphine and Met-enkephalin as affected by prolonged hydrocortisone and ACTH treatment

In the rats treated with ACTH or hydrocortisone for 14 days the catalepsy induced by morphine was almost completely inhibited, while the haloperidol induced catalepsy remained unchanged. The morphine induced hypermotility was altered neither by prolonged treatment with ACTH nor by an acute glucocorticoid administration. Inhibition of Na/K ATPase by ouabain led to an increase of striatal acetylcholine (Ach) release, which was enhanced by Met-enkephalin. This effect of the opioid peptide was not demonstrable in the striata of ACTH or hydrocortisone pretreated rats. It is concluded that glucocorticoids are regulatory factors of the striatal opiate neurotransmission possibly via altered receptorial mechanisms.     

Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex

Using microdialysis in rat prefrontal cortex, we found that 1 mg/kg of the stimulant methylphenidate and the non-stimulant atomoxetine, two widely used treatments for Attention Deficit/Hyperactivity Disorder (ADHD), produce robust increases in the extracellular levels of histamine, which plays a key role in attention, learning and memory. While the clinical response to ADHD drugs is typically attributed to modulation of norepinephrine and dopamine, this finding suggests enhanced histamine release may contribute to their efficacy as ADHD treatments.     

Mechanism of the body weight increase induced by systemic sulpiride

Long-term intraperitoneal administration of sulpiride induced body weight increase in female but not in male rats. The hypothesis that systemic sulpiride causes an endocrine unbalance which in turn causes body weight gain and hyperphagia was tested in four experiments. First, it was shown that even when they are on a high-fat diet male rats do not show body weight gain induced by systemic sulpiride. Second, sulpiride suppressed the estrous cycle. Third, gonadectomy prevented the body weight gain induced by systemic sulpiride in female rats. Fourth, estradiol simultaneously administered with sulpiride prevented the expected sulpiride-induced body weight gain. These results are discussed in terms of an hypothetical functional castration produced by systemic sulpiride. The well known hyperprolactinemia, induced by the pituitary D2 dopamine receptor blockade, might bring about an impairment of the steroidogenesis with subsequent decrease in estrogens level, which in turn might be responsible for the hyperphagia and body weight increase induced by systemic injections of sulpiride.     

Characterization of histamine release induced by fluoroquinolone antibacterial agents in-vivo and in-vitro

Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro. Intravenous injection of levofloxacin and ciprofloxacin at 1-10 mg kg(-1) produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg(-1), whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells. These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones.     

Endotoxins release histamine by complement activation and potentiate bacteria-induced histamine release

The histamine-releasing capability of bacterial lipopolysaccharides (LPS) was examined in human leukocyte suspensions. LPS alone did not release histamine, but it was found to enhance the histamine release caused by bacteria in basophils from persons sensitized to these bacteria. In the presence of serum, LPS was able to release histamine through complement activation. It is speculated that endotoxins reinforce release of histamine caused by bacteria in persons sensitized to these microorganisms, and a direct mediator release via complement activation might play a role in septic conditions.     

氯胺酮对术中应用芬太尼导致的术后吗啡需求增加的抑制作用

目的：旨在观察氯胺酮对术中应用芬太尼导致的术后吗啡需求增加的影响。方法：采用双盲方法将60例拟在腰麻下行开腹子宫切除术的患者随机分为4组：对照组（生理盐水,C）、芬太尼组（单次给予芬太尼1μg／kg,共3次,间隔15min,F）、氯胺酮组（切皮至手术结束前20min连续输注氯胺酮15μg·kg^-1·min^-1,K）、氯胺酮及芬太尼组（切皮至手术结束前连续输注氯胺酮15μg·kg^-1·min^-1;术中单次给予芬太尼1μg／kg,共3次,间隔15min,FK）。于术后1、3、6、12、24及48h记录累计吗啡需要量、痛觉评分及药物副作用（恶心、呕吐、幻觉、头晕、头痛及皮肤瘙痒）。结果：共60例患者入选本研究。4组患者的年龄、体重、手术持续时间及术后感觉阻滞时间差异无统计学意义。F组术后3、6、12h的累计吗啡需要量显著高于C组（P〈0．05）。C组、K组及FK组患者在术后各时间点的累计吗啡需要量差异无统计学意义。各组患者的术后痛觉评分差异无统计学意义。K组及FK组患者的术中及／或术后幻觉发生率显著高于C组（P〈0．05）。结论：本研究结果显示术中使用芬太尼可导致患者术后吗啡消耗量增加,而预先使用N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂氯胺酮可预防芬太尼的以上作用。     

吗啡与丁丙诺啡的蛛网膜下腔与皮下联合给药的相互作用(英文)

目的:观察大鼠吗啡与丁丙诺啡(或吗啡)的蛛网膜下腔与皮下联合给药的相互作用。方法:SD大鼠,置入蛛网膜下腔导管。辐射热诱发鼠腿撤退试验测痛阈。分别蛛网膜下腔给予吗啡、皮下注射丁丙诺啡(或吗啡)、蛛网膜下腔给予吗啡与皮下注射丁丙诺啡(或吗啡)的联合给药。结果:单独和联合给药均剂量依赖性地提高鼠痛阈。联合给药的量效曲线的斜率均显著大于吗啡单独给药的曲线斜率。等效线图显示联合给药的ED_(50)均位于理论推测的叠加效应线的左侧。结论:吗啡与丁丙诺啡(或吗啡)的蛛网膜下腔与皮下联合给药呈协同效应。