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T Wenger

Publications and source records attributed to T Wenger.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cannabinoid receptor binding did not vary in several hypothalamic nuclei after hypothalamic deafferentation.

Cannabinoid receptors are sparsely distributed in the hypothalamic nuclei, although they seem to be located on key neurons because their activation produces important neuroendocrine effects. In the present study, we have examined whether cannabinoid receptor-containing hypothalamic neurons are intrinsic or extrinsic to this brain region. To this end, we have examined whether the hypothalamic deafferentation was followed by a general loss of cannabinoid receptor binding, thus suggesting that cannabinoid receptor-containing neurons would have their cell bodies outside the hypothalamus, or whether this was followed by no changes in binding, thus suggesting that cannabinoid receptors would be located on intrinsic neurons. Three experimental groups were then analyzed: (i) animals with complete hypothalamic deafferentation in both sides; (ii) hemideafferentated animals; and (iii) sham-operated animals. In the three cases, cannabinoid receptor binding did not vary among these three groups in any of the hypothalamic nuclei analyzed. These were the arcuate nucleus, ventromedial hypothalamic nucleus, lateral and dorsal hypothalamic areas, paraventricular nucleus and medial preoptic area. This clearly supports the view that cannabinoid receptor-containing neurons into the hypothalamus are all intrinsic to this brain region.

Animals↗
PubMed1997

Arachidonyl ethanolamide (anandamide) activates the parvocellular part of hypothalamic paraventricular nucleus.

Arachidonyl ethanolamide, anandamide (ANA) was administered to male rats via a single i.p. injection at a dose of 0.02 mg/kg. In an parallel experiment ANA injection was preceded by the injection of SR 141716 (1.0 mg/kg), a selective and potent cannabinoid receptor antagonist. We observed using FOS protein immunocytochemistry that the parvocellular part of hypothalamic paraventricular nucleus (PVN) was activated as soon as 45 min. after ANA injection, i.e. the PVN showed an increased FOS immunoreactivity (FOSir). The peak level of FOSir was observed 90 min, after treatment. Meanwhile serum ACTH and corticosterone levels, as measured by radioimmunoassay, also significantly increased. 180 min. following drug injection both FOSir and serum hormone levels and returned to normal. SR 141716 did not antagonize these effects of ANA. We postulate that the locus of action of ANA the activation of the hypothalamo-pituitary-adrenal (HPA) axis is the parvocellular part of PVN. This activation may occur via a possible central cannabinoid receptor for which SR 141716 is not an effective antagonist. The rapid central response and activation of the HPA axis further support the view that ANA may be a central neurotransmitter or neuromodulator.

Adrenocorticotropic Hormone↗
PubMed1997

Effects of anandamide on gestation in pregnant rats.

The present study was to test whether the recently described endogenous ligand for the cannabinoid receptor; arachidonyl-ethanolamide (anandamide, ANA), may produce similar effects on pregnancy as the main psychoactive component of marihuana: delta9-tetrahydrocannabinol (THC) in rats. ANA, THC (0.02 mg/kg i.p./day, respectively) or vehicle were injected daily over the third week of pregnancy. The pregnant rats were either killed on day 21 of pregnancy or followed up to delivery. Results show a significant increase in the duration of pregnancy after both THC and ANA treatment. Both drugs caused an increase in the frequency of stillbirths. The mothers' hormone contents in tissues and sera were measured. Decreased LH content was observed in the serum of treated animals. No changes in FSH content were observed either in the pituitary or in the sera. Pituitary prolactin (PRL) levels was lower in ANA treated animals as compared both to controls or THC treated subjects. The serum PRL content decreased in all experimental groups. Decrease in serum progesterone was more prominent in treated rats. Serum levels of prostaglandins (PGF 1alpha and PGF 2alpha) were significantly decreased after THC and ANA treatment. We conclude that ANA has the same tendency to change reproductory parameters in pregnant rats as THC, although in some cases the effects of ANA were slightly different from that of THC. Both endogenous and exogenous cannabinoids inhibit PG synthesis in pregnant rats and this maybe responsible for the delay constitute the mechanism in the onset of labour.

Animals↗
PubMed1997

The effects of prenatally administered endogenous cannabinoid on rat offspring.

We reported previously that the main psychoactive component of marihuana, delta9 tetrahydrocannabinol (THC), when injected prenatally, temporarily inhibited the developing hypothalamo-pituitary system in rat offspring. In the present study, we investigated the effects of the recently described endogenous ligand for the central cannabinoid receptor, arachidonyl-ethanolamide (anandamide, ANA), on the postnatal development of the hypothalamo-pituitary axis (HPA) when administered during the third week of gestation. Rat pups were killed every fifth day from delivery to the 20th postnatal day; gonads, pituitary, and rest of body were weighed, and samples were collected for analysis of gonadotropin releasing hormone in the hypothalamus and luteinizing hormone, follicle stimulating hormone, prolactin, and growth hormone in the pituitaries and sera. The effects of ANA and THC were compared. Both ANA and THC caused predominantly inhibitory effects on the measured parameters. The inhibition was most pronounced immediately following delivery, whereas at the end of the investigated period (20th postnatal day) no differences were observed. We conclude that endogenous and exogenous cannabinoids have similar but slightly different effects on the developing HPA and that the action is transitory. We postulate that ANA probably acts via central cannabinoid receptors and/or neuroendocrine receptors to function as a neuromodulator.

Age Factors↗
PubMed1996

Triterpenes as potential dimerization inhibitors of HIV-1 protease.

HIV-1 protease is a homodimeric enzyme. A beta-sheet consisting of the four terminal segments provides the main driving force for dimerization of the per se inactive protomers. Several short peptides with sequences related to the terminal sequences of the protease are able to inhibit dimerization by blocking the 'interface' part of the monomers. From the structures of such inhibitory peptides a 'pharmacophore' could be derived. By using a prominent distance from this pharmacophore scaffold for a library search (Cambridge Structural Database), non-peptide inhibitors of HIV-1 protease with polycyclic triterpene structure could be found. The IC50 constants of these compounds are near 1 microM. One of the triterpenes, the ursolic acid (Ki = 3.4 microM), was further kinetically analysed (according to Zhang). The shape of the graph confirms the expected mechanism of dimerization inhibition.

Amino Acid Sequence↗
PubMed1996

The inhibition of human immunodeficiency virus proteases by 'interface peptides'.

The active human immunodeficiency virus type 1 (HIV-1) protease has a homodimeric structure, the subunits are connected by an 'interface' beta-sheet formed by the NH2- and COOH-terminal amino acid segments. Short peptides derived from these segments are able to inhibit the protease activity in the range of micromolar IC50 values. We have further improved the inhibitory power of such peptides by computer modelling. The best inhibitor, the palmitoyl-blocked peptide Pam-Thr-Val-Ser-Tyr-Glu-Leu, has an IC50 value of less than 1 microM. Some of the peptides also showed very good inhibition of the HIV-2 protease. The C-terminal segment of the HIV-1 matrix protein, Acetyl-Gln-Val-Ser-Gln-Asn-Tyr, also inhibits HIV-1 protease. Kinetic studies confirmed the 'dissociative' mechanism of inhibition by the peptides. Depending on the peptide structure and ionic strength, both dimerization inhibition and competitive inhibition were observed, as well as synergistic effects between competitive inhibitors and interface peptides.

Antiviral Agents↗
PubMed1995

Effects of anandamide (endogen cannabinoid) on anterior pituitary hormone secretion in adult ovariectomized rats.

It has been shown that the main psychoactive component of marihuana, delta 9-tetrahydrocannabinol (THC) has mainly inhibitory effects on pituitary luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) and has no or little effect on follicle stimulating hormone (FSH) secretion. Recently the purification and availability of the putative endogenous ligand for the cannabinoid receptor, anandamide (arachidonyl ethanol-amide, anandamide) (ANA) provided us the opportunity to compare the effects of THC and ANA on the female neuroendocrine system in ovariectomized (OVX) rats. OVX was performed three weeks prior to the experimental period to avoid cyclic differences. OVX rats were injected i.p. with either THC or ANA (0.02 mg/kg.b.w./day, respectively) or vehicle for two weeks. The results show that both ANA and THC decrease serum LH level although THC with a higher degree. No significant differences were observed in serum FSH level. Both drugs decreased serum PRL. Serum GH was increased after THC administration and significantly decreased after ANA. The results indicate that ANA and THC alter pituitary hormone secretion, mainly by inhibitory action. The site of action requires further investigations.

Animals↗
PubMed1994

Cellular distribution of G protein Go alpha in pituitary lactotrophs: effects of dopamine.

Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. The exact mechanisms of G proteins action are still under investigation but they appear to involve effectors located in the plasma membrane as well as in other parts of the cell. With this study, we investigated the cellular and ultrastructural localization of G protein subunits, and particularly of Go alpha, in normal rat anterior pituitaries and in estrone-induced rat adenomatous lactotrophs. We also evaluated the effects of Go alpha cellular redistribution in rat adenomatous lactotrophs following short-term exposure to dopamine (DA). Using the Protein A-gold (PAG) methodology, Go alpha was found to be present in the cysternae of the endoplasmic reticulum of normal pituitary cells and of adenomatous lactotrophs. In the latter, Go alpha could be co-localized with prolactin (PRL). By immunoblots, using specific antisera, significant amounts of Go alpha and Gs42 alpha, together with smaller amounts of Gi alpha, Gs47 alpha and G beta were found to be present in the uncontaminated supernatant fraction of adenomatous lactotrophs. Unexpectedly, exposure of the cells to DA induced a rapid and short-lived decrease in the cytosolic fraction of Go alpha and G beta associated with a decrease of PRL release. Since cytosolic Go alpha can be ADP-ribosylated by pertussis toxin (PT) and is therefore in a heterotrimeric form, our data suggest that the soluble Go protein may play a role during lactotrophs' exposure to an inhibitor of PRL release, perhaps through its relocalization after being internalized with the D2 receptor or by being used for interaction with intracellular and/or membrane-bound effectors.

Adenoma↗
PubMed1993

[Not Available].

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Academies and Institutes↗
PubMed1992

The use of digoxin-specific Fab fragments for severe digitalis intoxication in children.

BACKGROUND: Because life-threatening digitalis intoxication is unusual in children, treatment with digoxin-specific-antibody Fab fragments (Fab) has rarely been reported. We describe the efficacy of Fab in the treatment of children with severe digitalis intoxication. METHODS: Twenty-nine children with intoxication due to digoxin (28) or digitoxin (1) received Fab at 21 participating hospitals between 1974 and 1986. Data were gathered about the patients' medical illnesses, doses and serum concentrations of digitalis, responses to Fab therapy, and outcomes. RESULTS: In the infants and young children with acute digoxin intoxication, the digoxin doses ranged from 0.30 to 0.96 mg per kilogram of body weight; two adolescents had severe intoxication after doses of only 0.20 and 0.26 mg per kilogram. The serum digoxin concentrations ranged from 3.0 to greater than 100 ng per milliliter (mean, 13.8). Atrioventricular block (present in 22 patients [76 percent]) was the most common sign of toxicity. All the patients in this series had severe disturbances of cardiac rhythm, hyperkalemia (mean serum potassium concentration, 5.4 mmol per liter), or both. In 27 patients (93 percent), digitalis toxicity resolved after the administration of Fab. Of the 19 patients for whom data were available on the timing of the response to Fab, 15 responded within 180 minutes. Three patients required retreatment with Fab. Seven died of complications unrelated to the administration of Fab. CONCLUSIONS: We recommend that Fab be used in the treatment of digitalis poisoning in infants and young children who have ingested greater than or equal to 0.3 mg of digoxin per kilogram, who have underlying heart disease, or who have a serum digoxin concentration of greater than or equal to 6.4 nmol per liter (greater than or equal to 5.0 ng per milliliter) in the elimination phase; and who also have a life-threatening arrhythmia, hemodynamic instability, hyperkalemia, or rapidly progressive toxicity. Adolescents, who are more sensitive to the toxic effects of digoxin than younger children, may require treatment with Fab after ingesting lower doses.

Acute Disease↗
PubMed1992

[Marijuana and reproduction. Effects on puberty and gestation in female rats. Experimental results].

The main psychoactive component of marihuana, delta-9-tetrahydrocannabiol (THC), was investigated at low doses (1 microgram/kg/day) on the onset of puberty, on the reproductive functions in female rats up to the seventy fifth to eightieth day of life as well as during the pregnancy. The administration of THC caused a delay of the onset of puberty, and the number of ova on the day of first estrus was significantly lower in treated animals. After puberty, alterations occurred in the neuroendocrine functions of animals received THC: estrous cycles were irregular, serum LH level was decreased. When THC was injected during the third week of pregnancy it caused a significant prolongation of the gestation period. There was 30% stillbirths (v.s. 3% in physiological saline treated rats). No teratological effects were observed. Serum LH, progesterone and prostaglandin contents were decreased. The results indicate that marihuana causes alterations in reproductive functions. The importance of fight against drug abuse is emphasized.

Animals↗
PubMed1991

Prenatally administered delta-9-tetrahydrocannabinol temporarily inhibits the developing hypothalamo-pituitary system in rats.

We have reported earlier that delta 9-tetrahydrocannabinol (THC) if injected over the 3rd week of pregnancy with a daily dose of 1 micrograms/kg b.wt., caused a significant prolongation of pregnancy and 42% of stillbirths, although no teratological effects were observed. In the present study, we investigated the postnatal development of hypothalamo-hypophyseal-gonadal axis of the above mentioned rats' living litters. The rats were killed every 5th day between the delivery (D0) and the 20th postnatal day (D20). The weight of the body and the gonads was measured and hormonal parameters were registered by RIAs. The body weight was lower in treated animals, with a higher degree in males. The weight of the gonads also decreased. Serum testosterone levels were lower in rats from D0 till D10, while at D15 and D20 no differences were recorded between controls and treated rats. No significant differences were observed in serum estrogen levels during the investigated period. Serum progesterone decreased up to D10. Pituitary luteinizing hormone (LH) diminished postpartum in both sexes up to D5. From D0 till D5, serum LH increased in males while it decreased in females. Hypothalamic luteinizing hormone releasing hormone decreased up to D15 in both sexes, less markedly in females than in males. The neuropeptide Y content of the hypothalamus was also decreased in early postnatal age. We concluded that a very low dose of prenatally administered THC caused transitory inhibition of the developing hypothalamo-pituitary-gonadal axis, i.e., postnatal changes were evoked in the neuroendocrine system. By the 20th postnatal day this effect of THC seemed to be eliminated.

Animals↗
PubMed1988

The effect of chronic prepubertal administration of marihuana (delta-9-tetrahydrocannabinol) on the onset of puberty and the postpubertal reproductive functions in female rats.

The effect of the main psychoactive component of marihuana, delta-9-tetrahydrocannabinol (THC) was investigated on the onset of puberty and on the reproductive function in female rats up to the seventy-fifth to eightieth day of life. The drug was administered i.p. at a dose of 1 microgram/kg/day between the twenty-second postnatal day and the day of vaginal opening (V.O.). The administration of THC caused a 2-day delay in V. O., and the number of ova on the day of first estrus was significantly lower in treated rats than in controls. No differences were observed in serum gonadotropin and prolactin (PRL) levels on the day of V. O. After puberty, alterations occurred in the neuroendocrine functions of animals receiving THC that persisted until adulthood: estrous cycles were irregular, the number of ova in animals killed 35-40 days after V. O. was reduced, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased (diminution of serum FSH content was less expressed). An increase in serum PRL concentration could be demonstrated only in animals killed on the day of estrus. From these results, it might be concluded that THC administered to prepubertal rats--even in a very low dose--causes long-term irreversible alterations in reproductive functions. The importance of the fight against drug abuse is emphasized.

Animals↗
PubMed1988

Hypothalamic action of delta-9-tetrahydrocannabinol to inhibit the release of prolactin and growth hormone in the rat.

The site of action of delta-9-tetrahydrocannabinol (THC) to inhibit the release of prolactin (PRL) and growth hormone (GH) was examined by in vivo and in vitro experiments. In conscious freely moving animals bearing implanted third ventricular (3V) and external jugular cannulae, THC or the diluent was microinjected into the 3V and blood samples were removed to determine the effect on plasma PRL and GH. Both the 0.4- and 4-micrograms dose injected intraventricularly resulted in a suppression of PRL and GH release as indicated by declines in plasma levels within 40-80 min which were highly significant statistically but not dose-related. The higher dose evoked a pulse of GH and/or PRL in most animals which preceded the lowering of hormonal levels. In the in vitro experiments dipersed anterior pituitary cells were incubated with 5 x 10(-8) or 5 x 10(-9)M THC or the diluent for 5 days. Fresh culture medium was added to the cells after 3 days and the cells cultured for an additional 2 days. After this period, the cells were incubated for an additional 2 h in culture medium with or without THC plus a near maximal dose of thyrotropin-releasing hormone and GH-releasing factor (50 and 10 ng/ml, respectively) or the diluent to evaluate the response of PRL and GH release, respectively. Neither dose of THC altered the release or storage of the two hormones during culture or affected the response to the releasing hormones which is suggestive that there is no direct effect of THC on either GH or PRL release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of delta-9-tetrahydrocannabinol on the hypothalamic-pituitary control of luteinizing hormone and follicle-stimulating hormone secretion in adult male rats.

The main psychoactive component of marihuana, delta-9-tetrahydrocannabinol (THC) was injected into the 3rd cerebral ventricle. A single dose of THC (2 microliter of 10(-6) M) decreased serum LH temporarily but did not alter serum follicle-stimulating hormone (FSH) levels. The mediobasal hypothalamic (MBH) luteinizing hormone-releasing hormone (LHRH) content was elevated by 30 min after the injection. The elevation persisted for 1 h. Then, the LHRH content returned towards the preinjection level. In contrast, the LHRH in the organum vasculosum of the lamina terminalis did not change after a single dose of THC. The results indicate that THC alters pituitary LH release by inhibiting the release of LHRH which then increases in the MBH by continued synthesis or transport from rostral areas. In addition, the data support the existence of an FSH releasing factor, the release of which is not suppressed by this dose of THC. THC did not alter the release, storage or responsiveness to LHRH of cultured anterior pituitary cells, which further supports the view that its principal site of action is on the hypothalamus.

Animals↗