Biomedical subjects

L Busch

Publications and source records attributed to L Busch.

At least 19 recordsLinked to original sources

PubMed2006

Endogenous signalling system involved in parotid gland adenosine A(1) receptor-amylase release.

AIM: In this study, we have determined signalling pathways involved in adenosine A(1) receptor (A(1) receptor)-dependent stimulation of amylase release in rat parotid gland. METHODS: Amylase release, binding and cyclic adenosine monophosphate (cAMP) assays, inositol phosphates (IPs) production and nitric oxide synthase (NOS) activity in the presence of cyclopentyl-1,3-dipropylxanthine (CPA) alone or in the presence of different inhibitory drugs were performed. RESULTS: The binding parameters of specific A(1) antagonist [(3)H]-cyclopentyl 1,3-dipropilxanthine ([(3)H]-DPCPX) in parotid gland membranes show a population of high affinity sites with K(d) (nm) 0.53 +/- 0.06 and B(max) (fmol mg(-1) protein) 122.6 +/- 10.2. CPA stimulation of A(1) receptor exerts an increase in amylase release, IPs accumulation, cAMP production and NOS activity. All these A(1) agonist effects were blocked by the A(1) receptor antagonist DPCPX. Inhibitors of phospholipase C (PLC), calcium/calmodulin (CaM), protein kinase C (PKC), and adenylate cyclase, but not NOS, activities attenuated the CPA stimulatory effect on amylase release. The effect of CPA on amylase release significantly correlated with its action either on cAMP or on IPs accumulation. CONCLUSION: These results suggest that CPA activation of parotid gland A(1) receptor induces a stimulatory effect on amylase release associated with increased production of cAMP and IPs accumulation. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via PLC activation. This, in turn, triggers cascade reactions involving CaM and PKC. The CPA stimulation of NOS does not appear to participate in amylase release.

Adenosine A1 Receptor Antagonists↗

PubMed2002

Nitric oxide synthase/PGE(2) cross-talk in rat submandibular gland.

It is known that nitric oxide modulates the prostaglandin generation. However, little is known about the regulatory action of prostaglandin on nitric oxide production. There is a molecular cross-talk between nitric oxide and prostaglandin. Here, we examined biochemical signalling pathways coupled to the prostaglandin E(2) (PGE(2)) receptor related to nitric oxide synthase stimulation in rat submandibular gland. PGE(2) through the stimulation of its own receptor, triggered activation of phosphoinositide turnover (IPs), translocation of protein kinase C (PKC), stimulation of nitric oxide synthase activity (NOS) and increased production of cyclic GMP (cGMP). PGE(2) stimulation of NOS and cGMP production was blunted by agents interfering with calcium influx, calcium/calmodulin and phospholipase C (PLC) activities; while PKC inhibitor was able to stimulate PGE(2) effects. PGE(2) did not evoke amylase release, indicating that NOS/ cGMP pathway were not associated with this enzyme secretion. Our results suggest that this prostanoid could act as vasoactive chemical mediator through its ability to activate NOS-cGMP pathway via own gland membrane receptor.

Amylases↗

PubMed2001

The development of colon innervation in trisomy 16 mice and Hirschsprung's disease.

AIM: To study the colon innervation of trisomy 16 mouse, an animal model for Down's syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprung's disease (HD). METHODS: Trisomy 16 mouse breeding;cytogenetic analysis of trisomy 16 mice; and PG P9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS: Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was revealed in the stenosed segment of HD colon. CONCLUSION: Trisomy 16 mice could serve as an animal model for Hirschsprung's disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency.

Animals↗

PubMed2000

Fluoxetine modulates norepinephrine contractile effect on rat vas deferens.

The aim of this study was to evaluate whether the antidepressant drug fluoxetine could modify rat vas deferens response to norepinephrine (NE), and to compare its effect with that of desipramine and cocaine. Results showed that 10(-5)m fluoxetine produced a super-sensibility of vas deferens to NE. This result was the same as those obtained for 10(-6)m desipramine or cocaine. Since the effect was Na(+)- and Cl(-)-dependent, an inhibitory mechanism of neuronal NE transport was suggested. Fluoxetine did not modify [(3)H]prazosin K(d) or B(max) in rat vas deferens, reinforcing the hypothesis of a pre-synaptic site of action. On the other hand fluoxetine inhibited NE maximal effect. This inhibitory effect could be related to an antagonism of calcium entry through the voltage-dependent calcium channel, since it was partially reverted by increasing calcium concentration and, besides, the drug was able to inhibit the calcium concentration-response curve also. Contractions induced by 5-hydroxytryptamine (5-HT) were not modified in the presence of fluoxetine. It is concluded that fluoxetine modulates rat vas deferens response to low NE concentrations in the same manner as the selective inhibitor of NE neuronal uptake desipramine. This peripheral effect could participate in the modulation of the male reproductive tract observed by these drugs when used in clinical trials.

Animals↗

PubMed2000

Influence of castration on the response of the rat vas deferens to fluoxetine.

Antidepressant drugs such as desipramine and fluoxetine increase norepinephrine (NE) contractile response in rat vas deferens by inhibiting neuronal amine uptake. Fluoxetine, unlike other antidepressants, also inhibits calcium fluxes, which results in an inhibition of maximal NE effect. Since the contractile response of the reproductive tract is under the influence of testosterone, the effect of fluoxetine could be modified according to the endocrine status of the animal. In the present study we evaluated the influence of castration and testosterone replacement (1 mg per 100 g body wt.) on the peripheral action of fluoxetine. Castration was followed by a decrease in vas deferens weight and the appearance of spontaneous activity. Testosterone replacement reversed these effects. Concentration-response curves to NE and calcium were obtained in the absence and the presence of fluoxetine in vasa deferentia from normal, castrated and testosterone-treated castrated rats. After castration the effect of fluoxetine on vas deferens contractility was markedly altered. The spontaneous activity that appears after castration was prevented by fluoxetine and the stimulatory effect on NE-induced contractions was not observed. In contrast, the inhibitory action of fluoxetine on maximal NE effect was increased. Testosterone replacement restored vas deferens response to NE in the presence of fluoxetine. Fluoxetine did not modify the binding parameters of [(3)H]prazosin in vasa deferentia from normal or castrated animals. Cocaine shifted the NE concentration-response curve to the left in all groups, suggesting that the changes in fluoxetine effect following castration were not the result of an alteration of the neuronal uptake mechanism. The nitric oxide synthase inhibitor l-NMMA did not modify vas deferens response to NE in castrated animals either in the absence or presence of fluoxetine. An increased sensitivity to the inhibitory effect of fluoxetine was observed in the calcium concentration-response curves in vasa deferentia from castrated rats, an effect that was reversed by testosterone replacement. The results suggest that the alteration in the responsiveness of vasa deferentia from castrated rats to calcium could be responsible for increased sensitivity to the inhibitory effect of fluoxetine. It is concluded that vas deferens contractile response is testosterone dependent and that this behaviour modifies the effect of drugs such as fluoxetine that have dual effect on contractility.

Adrenergic alpha-Antagonists↗

PubMed1999

Long-term treatment with fluoxetine associates with peripheral effects on rat vas deferens contractility.

The aim of this work was to study whether long-term treatment with fluoxetine could induce peripheral effects by modifying vas deferens contractile activity. For this purpose the contractile response to NE, and 5-HT of vas deferens isolated from male Wistar rats that received fluoxetine 10 mg/kg/day i.p., during 21 days, was studied using the isolated organ bath technique. Results show that vas deferens of treated rats presented spontaneous activity, an effect that was abolished by prazosin and isoproterenol and that was not affected by nitroprusside or indomethacin. In addition, fluoxetine did not modify the response to calcium suggesting that spontaneous activity was not a consequence of an abnormal calcium movement. Fluoxetine induced a significant increase in the response of vas deferens to 5-HT and to low NE concentrations while NE maximal effect was unaffected. Fluoxetine treatment did not modify the binding parameters of [3H]-prazosin to vas deferens. It is concluded that long-term treatment with fluoxetine modifies vas deferens contractile activity. This effect could be the result of an alteration of adrenergic neurotransmission and could account for some of the untoward effects observed during clinical course with fluoxetine.

Adrenergic Agents↗

PubMed1999

[Observation on the development of stomach innervation in trisomy 16 mouse, an animal model for Down syndrome].

OBJECTIVE: To study the nervous development in the stomach of trisomy 16 mouse embryos and their normal littermates from embryonic days 13-18 (ED 13-ED 18) by using primary antibody against protein gene product (PGP) 9.5. METHODS: (A) trisomy 16 mouse breeding; (B) trisomy 16 mouse embryos were confirmed by examining their chromosomes; (C) PGP 9.5 immunohistochemical method. RESULTS: In normal littermates, the precursor cells from the neural crest migrated into stomach at ED13. Numerous nervous processes connected each other and formed early nervous networks at ED14. Original ganglia appeared in the muscular plexus with very simple arrangement at ED15. The developed myenteric and submucosal plexuses were found at ED16 and ED17 respectively. The myenteric plexus and the internal and external submucosal plexuses were differentiated at ED18. In comparison with the normal littermates, the trisomy 16 mice's stomach nervous development was much slower. Their immature neurons did not appear in the stomach until ED14; the development and differentiation of stomach nervous plexuses were delayed. A clear link was noted between the development of stomach plexuses and the density of PGP 9.5 immunostaining. A semiquantitative analysis and rank sum test of the data showed that the trisomy 16 mouse embryos were markedly retarded in nervous development of stomach, compared with their normal littermates (P<0.05). CONCLUSION: Trisomy 16 mouse, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in stomach innervation. This is the first report on delayed nervous development in the stomach of trisomy 16 mice.

Animals↗

PubMed1996

[Intraluminal expansion of a small intestine segment--animal experiment principles and possible clinical application].

In this study we expanded ileal segments of 8 pigs with an intraluminal expander over a period of 6 to 8 weeks till the volume had reached approximately sixfold of the starting volume. The morphological and morphometrical examinations showed flattened villi with elongated crypts and especially an increase in the thickness of the muscularis. The villi appeared flattened through scanning microscopy as well, but the structure of the microvilli was nearly normal. The proliferative activity in the muscularis, estimated immunohistochemically by a monoclonal antibody against PCNA, showed a threefold increase. So it can be assumed, that the increased thickness of the muscle layer was caused not only by muscle cell hypertrophy but also by hyperplasia. The activity of the alpha-glucosidase, a brush border enzyme, was clearly reduced. The minor cause of this effect was the direct damage of the microvilli from the expander, but the major cause was the exclusion of the ileal segment from the small bowel passage and the resulting lack of nutrients. With our technique it seems possible to create an ileum pouch, a stomach substitute or a urinary bladder substitute.

Animals↗

PubMed1996

Inhibitory effects of diazepam in rat vas deferens: role of calcium.

Diazepam and Ro5-4864 effects on noradrenaline-induced rat vas deferens contractions were studied. We investigated whether central or peripheral type benzodiazepine receptors were involved, by studying the effects of the selective central or peripheral benzodiazepine receptor antagonists, flumazenil (Ro 151788) or PK 11195 respectively. Diazepam interactions with GABA, adenosine, theophylline, and hypercalcic medium (3.5 mM) were studied. Also, we investigate diazepam effect on KCl depolarized vas deferens. Results showed that diazepam (10(-4) to 1.7 x 10 (-4) M) and Ro 5-4864 (10(-5) to 5.5 x 10(-5) M) inhibited NA-induced vas deferens contractions and that neither flumazenil nor PK 11195 antagonized diazepam or Ro 5-4864 inhibitory effects respectively. GABA, adenosine and theophylline did not modify neither NA vas deferens response nor diazepam inhibitory action. Diazepam effect was significantly reduced in and 3.5 mM calcium medium and KCl vas deferens response was inhibited by diazepam 1.3 x 10(-5) and 1.3 x 10(-4) M. It is concluded that in rat vas deferens diazepam effect seems to be related with calcium mobilization.

Adenosine↗

PubMed1993

Comparative effect of antiinflammatory drugs on rat paw edema induced by human sterile dental plaque extract, carrageenan or dextran.

The effect of antihistamine (diphenhydramine) or antihistamine and antiserotonin (cyproheptadine) or aspirin-like (acetylsalicylic acid and indomethacin) or corticosteroid (dexamethasone) drugs on the edema induced by various doses of carrageenan, dextran or human sterile dental plaque extract, injected intraplantarily in the rat paw were comparatively studied. The results showed that: (a) human dental plaque extract injected into the rat paw induces a dose-dependent inflammatory response, confirming that it is a potent phlogistic agent; (b) the edema induced by the plaque extract though closer to the pattern of carrageenan-induced edema, was different to both the carrageenan- and the dextran-induced edema in its time course and the response to antiedema drugs; (c) histamine and serotonin are liberated in the plaque-induced edema but they play no essential role; (d) the inhibitors of arachidonic acid metabolite formation (ASA, indomethacin and dexamethasone) inhibit this inflammation suggesting the presence of prostaglandin-like substances since its first phase.

Analysis of Variance↗

PubMed1993

Effects of calcium and its antagonists on histamine-induced leakage in rat skin.

Evans blue extravasation in rat skin was used to study the effects of calcium, lanthanum, L-type calcium channel blockers and trifluoperazine on histamine-induced leakage. Histamine effect was inhibited by calcium 1-2.5 mM, lanthanum 1-10 mM, nifedipine 0.1 and 1 microM and trifluoperazine 30 and 100 microM. The effects of calcium decreased progressively as its concentrations rose up to 10 mM. The association of nifedipine 0,1 microM or trifluoperazine 30 microM with calcium 3 microM increased the inhibitory effects. Calcium 10mM reversed the effect of nifedipine 0.1 microM but not that of lanthanum 1 mM or trifluoperazine 30 microM. It is proposed that the effect of calcium on histamine-induced leakage is the expression of a balance between an extracellular inhibitory effect and an intracellular enhancing effect.

Animals↗

PubMed1989

Effects of calcium and EDTA on rat skin capillary permeability and on its response to histamine, serotonin and bradykinin.

Evans blue extravasation in rat skin was used to study the effects of Ca2+ and EDTA on vascular permeability and on its response to mediators of inflammation. Ca2+ induced a concentration-dependent decrease of vascular permeability. The opposite effect was seen with EDTA 0.2 mM or higher. Effects on vascular permeability of intradermically injected histamine 100 micrograms/ml, serotonin 5 micrograms/ml and bradykinin 5 micrograms/ml, were lower when Ca2+ 8 mM was injected in the same site, and higher when EDTA 2 mM was given. EDTA effects were inhibited by Ca2+. The results suggest that, in rat skin, Ca2+ decreases capillary permeability and its response to histamine, serotonin and bradykinin.

Animals↗

PubMed1988

Lowered plasma erythropoietin in hypoxic rats with kidney tubule lesions.

The role of the kidney tubules in the renal formation of erythropoietin is incompletely understood. Therefore, the capability to produce erythropoietin in response to hypoxia was studied in rats with tubular lesions. Nephron damage was induced in two different ways. First, rats were treated with the nephrotoxic aminoglycoside gentamicin (67.5 mg/kg and day) for 14 days. The animals were then subjected to simulated altitude (6,800 m) for 6 h. The resulting plasma erythropoietin concentration was significantly lower (0.5 IU/ml) than in saline treated control rats exposed to hypoxia (1.0 IU/ml). Second, unilateral hydronephrosis was induced by ureteral ligation. The contralateral kidney was removed immediately before the animals were exposed to simulated altitude for 6 h. The plasma erythropoietin concentration in the ureter-ligated rats did not increase above the value (0.3 IU/ml) in hypoxia exposed anephric rats. These results indicate that the production of erythropoietin is reduced following tubular injury. Tubule cells may directly produce the hormone or interfere with the O2-sensing mechanisms controlling its synthesis. The latter hypothesis would seem to be supported by our failure to demonstrate in vitro erythropoietin production by the two established kidney tubule cell lines, LLC-PK1 and PK-15.

Altitude↗

PubMed1982