Effects of Guanethidine and Related Compounds on Histamine Excretion

1972 ◽  
Vol 50 (6) ◽  
pp. 539-544 ◽  
Author(s):  
J. LeBlanc ◽  
J. Côté ◽  
F. Doré ◽  
S. Rousseau

The basic nature of guanethidine and some of its effects suggested a possible action of this drug on histamine metabolism. A single intraperitoneal injection of guanethidine (10 mg/kg) in male rats was found to double the daily urinary excretion of free histamine; daily injection for three weeks caused a 10-fold increase. In male rats, guanethidine increased the number of mast cells in the peritoneal fluid and, in both peritoneal fluid and mesentery, caused a significant degranulation of these cells; this action was not observed in female rats. This finding may indicate that guanethidine blocks methylation of histamine by inhibiting imidazole methyl transferase since this enzyme is found in male but not in female rats. Bethanidine and reserpine had no effect on histamine excretion. Imidazole was found to be even more potent than guanethidine in causing an increase in urinary histamine. Guanethidine and imidazole neither potentiated nor mimicked the action of histamine on the isolated ileum.

1974 ◽  
Vol 61 (2) ◽  
pp. 344-358 ◽  
Author(s):  
Jarnardan K. Reddy ◽  
Daniel L. Azarnoff ◽  
Donald J. Svoboda ◽  
Jada D. Prasad

Nafenopin (2-methyl-2[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]-propionic acid; Su-13437), a potent hypolipidemic compound, was administered in varying concentrations in ground Purina Chow to male and female rats, wild type (Csa strain) mice and acatalasemic (Csb strain) mice to determine the hepatic microbody proliferative and catalase-inducing effects. In all groups of animals, administration of nafenopin at dietary levels of 0.125% and 0.25% produced a significant and sustained increase in the number of peroxisomes. The hepatic microbody proliferation in both male and female rats and wild type Csa strain mice treated with nafenopin was of the same magnitude and was associated with a two-fold increase in catalase activity and in the concentration of catalase protein. The increase in microbody population in acatalasemic mice, although not accompanied by increase in catalase activity, was associated with a twofold increase in the amount of catalase protein. The absence of sex difference in microbody proliferative response in nafenopin-treated rats and wild type mice is of particular significance, since ethyl-α-p-chlorophenoxyisobutyrate (CPIB)-induced microbody proliferation and increase in catalase activity occurred only in males. Nafenopin can, therefore, be used as an inducer of microbody proliferation and of catalase synthesis in both sexes of rats and mice. The serum glycerol-glycerides were markedly lowered in all the animals given nafenopin, which paralleled the increase in liver catalase. All the above effects of nafenopin were fully reversed when the drug was withdrawn from the diet of male rats. During reversal, several microbody nucleoids were seen free in the hyaloplasm or in the dilated endoplasmic reticulum channels resulting from a rapid reduction in microbody matrix proteins after the withdrawal of nafenopin from the diet. Because of microbody proliferation and catalase induction with increasing number of hypolipidemic compounds, additional studies are necessary to determine the interrelationships of microbody proliferation, catalase induction, and hypolipidemia.


2014 ◽  
Vol 115 (1-2) ◽  
pp. 43-59 ◽  
Author(s):  
Romana Šlamberová ◽  
Eva Macúchová ◽  
Kateryna Nohejlová ◽  
Andrea Štofková ◽  
Jana Jurčovičová

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.


1975 ◽  
Vol 65 (3) ◽  
pp. 389-397 ◽  
Author(s):  
K. BROWN-GRANT ◽  
FENELLA GREIG

SUMMARY Plasma FSH concentrations in rats have been determined by radioimmunoassay under a variety of experimental conditions to see whether any evidence could be obtained of an acute divergence in LH and FSH secretion rates which would support the idea of separate, specific hypothalamic releasing factors for these two hormones. During the normal ovarian cycle and after the administration of progesterone to female rats on the morning of the day of pro-oestrus increased secretion of both LH and FSH began simultaneously but FSH concentrations were later maintained or increased slightly while LH concentrations were falling. During early pregnancy FSH concentrations were higher than at the corresponding stage of the cycle at a time when LH concentrations had been shown to be lower. Progesterone injected at the dioestrous stage of the cycle reduced both LH and FSH concentrations though the effect on LH was more marked. After ovariectomy at any stage of the oestrous cycle or on day 4 of pregnancy there was a rapid and significant increase in plasma FSH concentration which was quite different from the delayed increase in LH concentration observed in these animals. In contrast, the early increase in FSH concentration in male rats after castration was less than the increase in LH concentration. The final FSH concentration in castrated males was only about four times the basal level in contrast to the 10- to 15-fold increase in LH in males and both LH and FSH in females. Anovulatory adult females that had received 1·25 mg of testosterone propionate on day 4 of postnatal life showed the rapid and sustained increase in plasma FSH after ovariectomy that was seen in normal females. None of these results strongly support the idea that separate and specific hypothalamic releasing factors for LH or FSH are secreted in the rat although the differences in the early response to gonadectomy could be explained on this basis.


1956 ◽  
Vol 187 (2) ◽  
pp. 307-311 ◽  
Author(s):  
James L. Leitch ◽  
Virginia G. Debley ◽  
Thomas J. Haley

Studies have been made on a spasmogen from rat urine. This material has been identified as histamine. It has been shown that both acute whole body x-ray irradiation and compound 48/80 significantly increase the quantity of endogenous urinary histamine. Endogenous histamine excretion in female rats is approximately 9–10 times greater than in male rats. Neither x-ray irradiation nor compound 48/80 elevate the amount of urinary histamine of the males to that of the female. Histamine liberation is of little or no importance insofar as lethality from acute whole body irradiation is concerned. The amount of histamine liberated by such irradiation is independent of radiation dosage within the range 600–1200 r. After radiation injury, significant levels of urinary histamine were detected only during the first 24 hours. Histamine depletion by chronic administration of compound 48/80 did not prevent further liberation of histamine by acute whole body irradiation. Irradiated animals are much more susceptible to the toxic effects of compound 48/80 than normal animals. Gonadectomy followed by α-estradiol injection did not increase the output of urinary histamine in male rats. Similar treatment of female rats with testosterone did not reduce their urinary histamine output, but a reduction was observed 140 days after surgery. Administration of cortisone acetate to male rats did not increase their excretion of endogenous histamine. Inactivation of diamine oxidase with aminoguanidine had little or no effect on urinary histamine output in male rats, but caused a threefold increase in females. Further elevation in urinary histamine was produced by irradiation or compound 48/80.


1961 ◽  
Vol 201 (4) ◽  
pp. 740-742 ◽  
Author(s):  
K. S. Kim

Urinary histamine output has been studied under various experimental conditions in rats. Orchidectomy increased the output of free histamine in rats of the Sprague-Dawley strain but not in rats of the Wistar strain. Subcutaneous administration of testosterone propionate (1 mg/rat) suppressed the output of free histamine in ovariectomized rats but not in normal females, which showed the effect only after repeated administration of this hormone. When exogenous histamine (100 µg) was administered at a constant rate over a 4-hr period, only a minute quantity of administered histamine appeared as free histamine in the urine of male rats. In contrast, 23% of administered histamine appeared as free histamine in the urine of female rats. When repeatedly treated with testosterone, female rats eliminated exogenous histamine more like males. The close relationship between testosterone and histamine metabolism in rats is thus clearly demonstrated.


1999 ◽  
Vol 162 (2) ◽  
pp. 177-187 ◽  
Author(s):  
GV Childs ◽  
G Unabia ◽  
BT Miller ◽  
TJ Collins

There is a 2- to 3-fold increase in luteinizing hormone-beta (LHbeta) or follicle-stimulating hormone-beta (FSHbeta) antigen-bearing gonadotropes during diestrus in preparation for the peak LH or FSH secretory activity. This coincides with an increase in cells bearing LHbeta or FSHbeta mRNA. Similarly, there is a 3- to 4-fold increase in the percentage of cells that bind GnRH. In 1994, we reported that this augmentation in gonadotropes may come partially from subsets of somatotropes that transitionally express LHbeta or FSHbeta mRNA and GnRH-binding sites. The next phase of the study focused on questions relating to the somatotropes themselves. Do these putative somatogonadotropes retain a somatotrope phenotype? As a part of ongoing studies that address this question, a biotinylated analog of GHRH was produced, separated by HPLC and characterized for its ability to elicit the release of GH as well as bind to pituitary target cells. The biotinylated analog (Bio-GHRH) was detected cytochemically by the avidin-peroxidase complex technique. It could be displaced by competition with 100-1000 nM GHRH but not corticotropin-releasing hormone or GnRH. In cells from male rats exposed to 1 nM Bio-GHRH, 28+/-6% (mean+/-s.d) of pituitary cells exhibited label for Bio-GHRH (compared with 0.8+/-0.6% in the controls). There were no differences in percentages of GHRH target cells in populations from proestrous (28+/-5%) and estrous (25+/-5%) rats. Maximal percentages of labeled cells were seen following addition of 1 nM analog for 10 min. In dual-labeled fields, GHRH target cells contained all major pituitary hormones, but their expression of ACTH and TRH was very low (less than 3% of the pituitary cell population) and the expression of prolactin (PRL) and gonadotropins varied with the sex and stage of the animal. In all experimental groups, 78-80% of Bio-GHRH-reactive cells contained GH (80-91% of GH cells). In male rats, 33+/-6% of GHRH target cells contained PRL (37+/-9% of PRL cells) and less than 20% of these GHRH-receptive cells contained gonadotropins (23+/-1% of LH and 31+/-9% of FSH cells). In contrast, expression of PRL and gonadotropins was found in over half of the GHRH target cells from proestrous female rats (55+/-10% contained PRL; 56+/-8% contained FSHbeta; and 66+/-1% contained LHbeta). This reflected GHRH binding by 71+/-2% PRL cells, 85+/-5% of LH cells and 83+/-9% of FSH cells. In estrous female rats, the hormonal storage patterns in GHRH target cells were similar to those in the male rat. Because the overall percentages of cells with Bio-GHRH or GH label do not vary among the three groups, the differences seen in the proestrous group reflect internal changes within a single group of somatotropes that retain their GHRH receptor phenotype. Hence, these data correlate with earlier findings that showed that somatotropes may be converted to transitional gonadotropes just before proestrus secretory activity. The LH and FSH antigen content of the GHRH target cells from proestrous rats demonstrates that the LHbeta and FSHbeta mRNAs are indeed translated. Furthermore, the increased expression of PRL antigens by these cells signifies that these convertible somatotropes may also be somatomammotropes.


1961 ◽  
Vol 201 (2) ◽  
pp. 224-226 ◽  
Author(s):  
K. J. Netter ◽  
V. H. Cohn ◽  
P. A. Shore

Female rats excrete much more free endogenous histamine than do males. The sex difference lies in histamine catabolism rather than biosynthesis, since females excrete, unchanged, a much higher percentage of injected histamine than do males. Investigation of the activity in vitro of the major histamine metabolizing enzymes, diamine oxidase (DAO) and imidazol-N-methyl transferase (IMT), showed no sex difference in distribution or activity, nor was there a sex difference in the activity of liver methionine-activating enzyme. Measurement of the biologic half-life of injected histamine revealed no sex difference in normal rats, in rats treated with the DAO inhibitor, aminoguanidine (AG), or in rats after nephrectomy, which removes almost all of IMT activity. A combination of AG and nephrectomy, however, resulted in a marked sex difference, which did not appear to be due to histamine conjugation or to liver drug-metabolizing enzymes. The findings suggest that male rats possess a minor histamine-metabolizing pathway which females lack.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.


2019 ◽  
Vol 20 (1) ◽  
pp. 75-84

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy


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