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At least 991 records · Page 55Linked to original sources
PubMed1993

Autoregulation of histamine synthesis through H3 receptors in isolated fundic mucosal cells.

Histamine plays an important role in the control of gastric acid secretion by activating H2 receptors located on parietal cells. In gastric mucosa, histamine is stored both in mast cells and in enterochromaffin-like cells, especially in rodents. It has been proposed that histamine may regulate its own synthesis and/or release through receptors pharmacologically distinct from H1- and H2-receptor subtypes. In this article, we studied the regulation by histamine of histidine decarboxylase (HDC) activity (enzyme responsible for the formation of histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)-alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/- 3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine-induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and 9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine) antagonists were unable to affect HDC activity. Moreover, high concentrations of thioperamide (1-10 microns) increased histamine release from these cells. All these results allowed us to conclude that, in gastric mucosa, histamine downregulates its own synthesis (and perhaps release) through the stimulation of autoreceptors with pharmacological characteristics of H3 receptors. However, the relationship between histamine synthesis and release remains unclear and needs further investigation.

Animals↗
PubMed1990

Brain histamine regulates pressor responses to peripheral hyperosmolality.

The role of brain histamine (HA) in the pressor response to peripheral hyperosmolality was investigated in the conscious Sprague-Dawley rat. Increased mean arterial pressure was observed during a 30-min intravenous infusion of hypertonic saline (HTS; 10 microliters.100 g body wt-1 x min-1) in vehicle-treated controls (20.1 +/- 3.8 mmHg) and in animals centrally pretreated with the specific H2-antagonist, cimetidine (15.0 +/- 3.7 mmHg). However, this pressor response was abolished in a dose-dependent manner after intracerebroventricular injection of the H1 antagonist promethazine. In other experiments, brain tissue microdissected from the supraoptic nucleus (SON), paraventricular nucleus (PVN), and posterior hypothalamic region showed significantly lower levels of total tissue HA after 60 min of intravenous HTS infusion compared with tissue taken from control animals receiving an isotonic infusion. Microdialysis in the region of the PVN or SON before and during HTS infusion showed increased extracellular concentrations of HA in the SON (24.4 +/- 10.9%) during infusion. No change in extracellular HA concentration was seen in the PVN during HTS infusion. These results support the conclusion that endogenous brain HA is involved in the pressor response to peripheral hyperosmolality.

Animals↗
PubMed1976

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.

Animals↗
PubMed1999

A comparison of the effect of three sedatives on esophageal sphincters in cats.

BACKGROUND/AIMS: Children 5 years old and younger often require sedation for esophageal motility studies (EMS). At our institution, an intramuscular cocktail of meperidine, promethazine and chlorpromazine (MPC) has been used as the standard sedative for young children undergoing EMS. Administering the intramuscular sedative may, however, be more traumatic to the child than the procedure. Moreover, its effect on esophageal motility is not known and prolonged sedation is common. The aim of this study was to determine the effects of MPC and two orally-administered sedatives on esophageal sphincter function, using the cat model, with a goal to identify a potentially suitable orally-administered sedative for use in young children requiring sedation for EMS. METHODS: We measured upper (UESP) and lower (LESP) esophageal sphincter pressures in 25 cats initially without sedation, and then following sedation with midazolam, chloral hydrate and MPC. The results were compared. RESULTS: All three sedatives significantly decreased LESP compared to the control (p<0.05). Midazolam decreased LESP the most; however, the difference from the other sedatives did not reach statistical significance. All three sedatives decreased UESP, compared to control, but the differences were not statistically significant. Of the two oral sedatives, chloral hydrate had the least effect on the esophageal sphincters although its effect was not statistically different from that of midazolam. CONCLUSIONS: Ethically appropriate studies are needed to determine which oral sedative would be most beneficial for use in sedating children undergoing esophageal motility studies. Until studies can be done, the choice between chloral hydrate and midazolam should be based on the experience and comfort of the attending physician with regard to the potential side effects of the medications.

Analgesics, Opioid↗
PubMedDate not supplied

The neuroleptic malignant syndrome: occurrence in a 15-year-old boy and recovery with bromocriptine therapy.

The neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to neuroleptic medication not previously described in the pediatric literature. It is characterized by hyperthermia, extrapyramidal disorders, decreased level of consciousness and autonomic dysfunction. A 15-year-old boy with acute lymphoblastic leukemia developed the NMS after a brief exposure to chlorpromazine and promethazine. He responded favorably to the dopamine agonist bromocriptine. A review of the recent literature suggests bromocriptine as the most efficacious specific therapy. Management of the NMS includes immediate discontinuation of all neuroleptic agents, intense supportive care and prompt institution of bromocriptine therapy.

Adolescent↗
PubMed1976

Vasopressin released by nicotine in the monkey.

The objective of this study was to determine the effects of i.v. nicotine on plasma arginine vasopressin (AVP), plasma osmolality, and behavior in the conscious monkey. Adult, female, chronically prepared monkeys (Macaca mulatta) were studied with i.v. infusion of 5% dextrose and water in control experiments without change in parameters. Nicotine infusion (100 mug/kg/min) in 14 experiments produced a significant increase in plasma AVP from control levels of 0.6 +/- 0.5 muU/ml to end-of-infusion levels of 35 +/- 17 muU/ml (p less than 0.001). During the 15-20 min of nicotine infusion, a behavioral sequence of restlessness, yawning, retching, salivation and chewing accompanied AVP release. Plasma osmolality remained unchanged. Pretreatment of the monkeys with promethazine (Phenergan) and diphenhydramine (Benadryl) at 1-5 mg/kg reduced both the plasma AVP increase and the behavioral effects. These results provide conclusive evidence that nicotine can release large amounts of AVP in the monkey.

Animals↗
PubMed1977

The possible role of vasoactive substances for the hemodynamic effects of rapidly injected antilymphocyte globulin.

A rapid intravenous injection of ALG into splenectomized dogs induced an almost complete elimination of lymphocytes and an extensive but partly reversible thrombocytopenia during which platelets were trapped in the lung. During this trapping there was a significant decrease in arterial blood pressure, pulmonary blood volume and cardiac output concomitant with a marked increase in the portal pressure. The pulmonary arterial pressure remained unchanged. The hemodynamic effects are probably caused by a release of vasoactive substances which induced a decreased venous return from splanchnic pooling and statis. Prostaglandins and histamine seem to play a dominant role, since Aspirin, promethazine and 48/80 markedly reduced the side-effects.

Anaphylaxis↗
PubMed1981

Lack of histamine involvement in parathyroid hormone hypotensive action.

Promethazine and cimetidine blocked the hypotensive actions of 2-pyridylethylamine, and H1 agonist and dimaprit, an H2 agonist, respectively, but not that of bovine parathyroid hormone fragment [bPTH-(1-34)]. Rats were treated repeatedly with the histamine releaser, compound 48/80, until the release could no longer produce a decrease in blood pressure. The hypotensive action of bPTH-(1-34) could still be seen. Rats with histamine partially depleted with one injection of compound 48/80 were injected with cimetidine and pyrilamine, and H1 antagonist, which together blocked the hypotensive action of subsequent injections of compound 48/80, but not that of bPTH-(1-34). These data suggest that the vasodilatory action of bPTH-(1-34) does not involve the release or action of histamine.

Animals↗
PubMed1992

Effect of substance P and Sar9Met(O2)11-substance P on cutaneous capillary permeability in guinea pig skin.

The purpose of this study was to assess the effect of several drugs on the increase in cutaneous capillary permeability induced by intradermal injection of substance P (SP) and Sar9Met(O2)11-SP in guinea pig skin. On the one hand, the increase in cutaneous capillary permeability was partly reduced by spantide, promethazine, atropine or SR 40037, an inhibitor of the angiotensin-converting enzyme. On the other hand, norepinephrine and B3824, a B2-antagonist of bradykinin, showed an enhancing effect. Our results suggest that the effect of SP and Sar9Met(O2)11-SP in guinea pigs is partly mediated by histamine and acetylcholine, and that there is a relationship between tachykinins and bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Depression of neutrophil chemotaxis in atopic individuals. An H2 histamine receptor response.

Neutrophil chemotaxis was compared in normal and atopic individuals using a modified Boyden chamber with as chemotactant, autologous serum either unactivated or activated by zymosan or an endotoxin-containing house dust preparation. A high incidence of defective leukotaxis was found in atopics when cells were opposed to activated serum. The cause of this abnormality is not intrinsic to the leukocytes since random migration and chemotaxis towards unactivated serum were comparable in normal and atopic subjects. The defect persisted when atopic leukocytes were opposed to activated normal serum and the chemotactic response of normal neutrophils was not imparied when tested against activated atopic serum. Leukotaxis was significantly depressed by incubating atopic leukocytes with allergen to which they were sensitized, suggesting an inhibitory effect of mediators of anaphylaxis. Histamine inhibited in vitro neutrophil chemotaxis in normal and atopic subjects. This inhibition was dose-related and significantly more pronounced in atopics. Incubation of atopic leukocytes with an H2 antagonist, cimetidine, was capable of enhancing their chemotactic responsiveness towards activated autologous serum to levels observed in normal controls. In the same conditions, an H1 blocker, promethazine, was without effect. These data indicate that the leukotactic dysfunction of atopic individuals results from an abnormal sensitivity of these leukocytes to histamine which, in the chemotactic chamber, may be released from basophils by products of complement activation and, in some experimental conditions, by antigen to which cells are sensitized.

Chemotaxis, Leukocyte↗
PubMed1986

Effects of thiazinamium chloride on histamine release from rat peritoneal mast cells and on phosphodiesterase activity in guinea pig lung.

The effect of thiazinamium Cl (TCl) on histamine release from rat peritoneal mast cells (RPMC) was investigated. Although TCl inhibited compound 48/80-induced histamine release moderately (IC50 value 40 microM), the drug was a weaker inhibitor of ovalbumin-induced histamine release (100 microM, -21%). In contrast, promethazine HCl (PHCl) was more effective against antigen-induced histamine release (IC50 value 13 microM) than against compound 48/80-induced histamine release (100 microM, -53%). Disodium cromoglycate (DSCG) was effective against both antigen and compound 48/80-induced release of histamine with IC50 values of 7 and 1 microM, respectively. Neither TCl nor DSCG at 1 mM increased spontaneous release of histamine from RPMC, whereas PHCl induced spontaneous release by over 50% at 1 mM. TCl did not inhibit phosphodiesterase (PDE) activity in guinea pig lung at 1 mM, whereas theophylline and DSCG inhibited PDE with IC50 values of 1.1 and 0.32 mM, respectively. These data suggest that high local concentrations of TCl may reduce histamine release during an asthmatic attack and improve its effectiveness as a bronchoprotectant.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Effect of histamine on tumor necrosis factor production by human monocytes.

This study was aimed at evaluating the effect of histamine on tumor necrosis factor (TNF alpha) secretion by purified human blood monocytes. TNF alpha was measured by radioimmunoassay. Histamine caused a dose-dependent inhibition of lipopolysaccharide-induced TNF alpha production from human blood monocytes, averaging maximally 50% at 10(-5) M. Preincubation of mononuclear cells with an H2 antagonist (cimetidine), but not with an H1 antagonist (promethazine) prevented this inhibitory effect of histamine. In conclusion, histamine causes, in vitro, a depression of TNF alpha secretion by human monocytes through activation of H2 receptors.

Adult↗
PubMed1974

The cardiovascular effects of morphine. The peripheral capacitance and resistance vessels in human subjects.

To evaluate the effects of morphine on the peripheral venous and arterial beds, 69 normal subjects were evaluated before and after the intravenous administration of 15 mg morphine. Venous tone was determined by three independent techniques in 22 subjects. The venous pressure measured in a hand vein during temporary circulatory arrest (isolated hand vein technique) fell from 20.2+/-1.4 to 13.4+/-0.9 mm Hg (P < 0.01) 10 min after morphine, indicating that a significant venodilation had occurred. With the acute occlusion technique, morphine induced a reduction in forearm venous tone from 12.8+/-1.1 to 7.9+/-2.3 mm Hg/ml/100 ml (P < 0.01). Although forearm venous volume at a pressure of 30 mm Hg (VV[30]) was increased from 2.26+/-0.17 to 2.55+/-0.26 ml/100 ml, measured by the equilibration technique, the change was not significant (P > 0.1). Of note is that the initial reaction to morphine was a pronounced venoconstriction, demonstrated during the first 1-2 min after the drug. (Isolated hand vein pressure increased to 37.2+/-5.4 mm Hg, P < 0.01). This rapidly subsided, and by 5 min a venodilation was evident. Morphine did not attenuate the venoconstrictor response to a single deep breath, mental arithmetic, or the application of ice to the forehead when measured by either the isolated hand vein technique or the equilibration technique. To evaluate the effects of morphine on the peripheral resistance vessels in 47 normal subjects, forearm blood flow was measured plethysmographically before and 10-15 min after the intravenous administration of 15 mg of morphine. Although mean systemic arterial pressure was unchanged, forearm blood flow increased from 2.92+/-0.28 to 3.96+/-0.46 ml/min/100 ml (P < 0.01), and calculated vascular resistance fell from 42.4+/-5.2 to 31.6+/-3.2 mm Hg/ml/min/100 ml (P < 0.01). When subjects were tilted to the 45 degrees head-up position, morphine did not block the increase in total peripheral vascular resistance that occurs; however, it did significantly attenuate the forearm arteriolar constrictor response (before morphine, + 25.7+/-5.4; after morphine, + 13.7+/-5.3 mm Hg/ml/min/100 ml, P < 0.05). However, morphine did not block the post-Valsalva overshoot of blood pressure, nor did it block the increase in forearm vascular resistance produced by the application of ice to the forehead. Similarly, morphine did not block the arteriolar or venoconstrictor effects of intra-arterially administered norepinephrine. Morphine infused into the brachial artery in doses up to 200 mug/min produced no changes in ipsilateral forearm VV[30], forearm blood flow, or calculated forearm resistance. Intra-arterial promethazine, atropine, and propranolol did not block the forearm arteriolar dilator response to intravenous morphine; however, intra-arterial phentolamine abolished the response. These data suggest that in human subjects, morphine induces a peripheral venous and arteriolar dilation by a reflex reduction in sympathetic alpha adrenergic tone. Morphine does not appear to act as a peripheral alpha adrenergic blocking agent but seems to attenuate the sympathetic efferent discharge at a central nervous system level.

Adult↗
PubMed1992

Sedation of children for technical procedures: current standard of practice.

We sought to define the current standard of care for children undergoing sedation for painless diagnostic procedures by sending questionnaires to 284 pediatric residency program directors in North America. From the 89 responses, we determined that departments of pediatrics set sedation policies for children in most institutions, often with formal written guidelines for these procedures. Most require that children have some form of cardiorespiratory monitoring while under sedation and that they are attended by individuals trained in cardiorespiratory resuscitation until the child is fully recovered. The use of parents to transport and monitor the sedated child is uncommon, and total lack of monitoring is rare. Chloral hydrate in dosages of 25 mg/kg to 100 mg/kg is the most common drug used for sedation; DPT, a combination of parenteral Demerol (meperidine), Phenergan (promethazine), and Thorazine (chlorpromazine), at a maximum dose of 2 mg/1 mg/1 mg/kg is the second; and pentobarbital in a dosage of 5 mg/kg to 7 mg/kg is the third. These sedation regimens were associated with few serious side effects, except that two deaths were reported in infants with congenital heart disease who were sedated with DPT. We believe this survey may reflect the current standard of practice for sedation in North American infants and children undergoing diagnostic procedures.

Attitude of Health Personnel↗
PubMed2000

Prokinetic effects of erythromycin after antimotion sickness drugs.

Motion sickness and the antimotion sickness drugs scopolamine (SCP) and promethazine (PMZ) inhibit gastric emptying (GE). This study was conducted to determine if erythromycin would exert its well-known prokinetic effects in normal and motion-sick subjects given antimotion sickness drugs. Fifteen fasted volunteers (11 males, 4 females) participated in the study. In control tests, 8 subjects were given intramuscular (i.m.) saline (SAL, 0.5 ml), SCP (0.1 mg), or PMZ (25 mg). GE of liquid (300 ml) containing 1 mCi of Tc 99m diethylenetriaminepentaacetic acid (DTPA) was measured by sequential gastric scintigraphy 30 minutes after i.m. treatments. In other tests, GE was measured in 8 subjects after each i.m. treatment, followed 10 minutes later by 200 mg of erythromycin ethylsuccinate (ESS) suspension given orally. In a third group of tests, 7 subjects received an i.m. treatment, oral EES 10 minutes later, and were then brought to an advanced level of motion sickness short of vomiting. To induce motion sickness, blindfolded subjects made timed head movements while seated in a rotating chair. GE was measured immediately after rotation. GE half-life, rate constant, area under the curve (AUC), and lag time were calculated using conventional mathematical methods for analyzing exponential rate processes. GE parameters calculated for normal and motion-sick subjects given antimotion sickness drugs and EES were compared with those from subjects given i.m. treatments (control) only. In normal subjects, EES significantly (p < 0.05) increased the GE rate constant for all i.m. treatments and reduced the AUC for SAL, SCP, and PMZ by 49% (p < 0.05), 44% (p < 0.05), and 69% (p < 0.01), respectively. In motion-sick subjects, lag time was significantly (p < 0.05) increased, and the rate constant and AUC values were unchanged from control for all i.m. treatments. The authors conclude that oral EES reverses the gastrostatic actions of the antimotion sickness drugs but does not affect the inhibition of gastric emptying associated with motion sickness. The results suggest that motion sickness and antimotion sickness drugs reduce GE through different mechanisms.

Administration, Oral↗
PubMed1976

Arterial hypotension induced by horseradish peroxidase in various rat strains.

The influence of various commercial preparations of horseradish peroxidase upon the arterial pressure has been investigated using direct intra-arterial pressure recordings in Nembutal anesthetized rats of different strains. A marked hypotension was noted in Wistar and Sprague-Dawley rats when sufficiently high doses (5-10 mg/100 g body weight) were injected intravenously. This effect was observed with both highly purified (Sigma type VI, Boehringer Reinheitsgrad I) as well as less pure preparations (Sigma type II, Boehringer Reinheitsgrad II). Prior injection of promethazin, an antihistamine, prevented the drop in arterial pressure. Wistar/Furth rats appeared almost resistant to the hypotensive effect of Sigma preparations but developed moderate to marked hypotension with both types of Boehringer horseradish peroxidase. When instead of Nembutal, ether anesthesia was used only a transient mild hypotension developed and the animals recovered within 7-10 min. No effect was noted in Syrian hamsters receiving injections with the same doses of horseradish peroxidase. Electrophoresis revealed marked variations in the isozyme composition of different horseradish peroxidase preparations. Since the exact nature of the hypotensive agent remains unknown, it is suggested that the arterial pressure be monitored before extensive systematic application of this tracer in vascular permeability studies in rats.

Animals↗
PubMed2006

The effects of alpha1-acid glycoprotein on the reversal of chloroquine resistance in Plasmodium falciparum.

An in-vitro model based on the semi-automated microdilution technique has been developed for selecting compounds that might be used clinically for the reversal of chloroquine resistance. This was used initially to test the susceptibility of Plasmodium falciparum clone W2 to chloroquine (CQ). The model was then employed to investigate the effects of each of four resistance-reversing agents (verapamil, desipramine, chlorpheniramine and promethazine, at 1 microM) on this parasite's susceptibility to CQ, with and without alpha(1)-acid glycoprotein (AGP), at a patho-physiological concentration (1.25 g/litre), in the culture medium. In the absence of AGP, each of the resistance-reversing agents reduced the median inhibitory concentrations of CQ by 82%-97%, from a baseline value of about 94 ng/ml. In the presence of AGP, however, most of the resistance-reversing agents had much less effect. There appears to be competitive interaction between CQ, the resistance-reversing agents and AGP. The binding kinetics between CQ, resistance-reversing agents, AGP and other plasma proteins will clearly need to elucidated if clinically effective resistance-reversing agents are to be selected in vitro.

Animals↗
PubMed2003

Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways.

CRH plays a central role as a mediator of the hypothalamic-pituitary-adrenal axis and stress response and is a potent vasodilator. Previously, we have shown that CRH causes a gender-specific vasodilation in human skin, although the mechanism by which CRH operates is unclear. CRH causes mast cell degranulation in rat skin. As such, histamine and other mast cell-derived factors may be indirectly responsible for the vasodilatory effects of CRH, although CRH is also known to act directly on the vasculature. CRH-induced vasodilation in human skin was examined using laser Doppler flowmetry and iontophoresis in adult females. CRH (1 nM) was administered iontophoretically to the forearm, and blood flow was measured simultaneously in the same area by laser Doppler. CRH-induced dilation of the skin microvasculature was significantly reduced in the presence of the mast cell degranulation inhibitor, sodium cromoglycate, the histamine H(1)-antagonist, promethazine, or the H(2)-antagonist, ranitidine. CRH-induced dilation was also significantly reduced in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor, piroxicam. These findings provide novel evidence that CRH-induced vasodilation in human skin occurs via mast cell degranulation and is principally mediated by histamine and, to a lesser extent, by prostacyclin and nitric oxide.

Cell Degranulation↗