摘要:

To get information about the peptide hormone receptors involved in duodenal bicarbonate secretion (DBS) and their cellular location, we determined DBS and adenylate cyclase (AC) activity in response to hormones of the vasoactive intestinal polypeptide (VΙP)&slash;secretin family of peptides. DBS was determined in an isolated, perfused (24 mmol/l NaHCO3) loop of the proximal duodenum in urethane- and indometacin-treated guinea pigs. AC stimulation was measured in isolated, homogenized duodenal enterocytes, the histological evaluation of which revealed their villous origin. VIP (10–9 to 10–7 mol × kg–1) dose-dependently increased DBS 3.5-fold (p < 0.01); this effect was completely inhibited by the VIP antagonist [D-p-Cl-Phe6, Leul 7]VIP (10–6 mol × kg–1). Glucagon (10–8 to 10–6 mol × kg–1) increased DBS 2.1-fold, while secretin (10–9 to 10–6 mol × kg–1) had no effect on DBS, but stimulated pancreatic bicarbonate secretion. VIP concentra-tion-dependently increased AC activity 5.6-fold with an EC50 of 1.3 × 10–9 mol/l. [ D-p-Cl-Phe6, Leul 7] VIP caused a right-ward shift of the VIP concentration-response curve. A Schild plot analysis yielded a slope of 0.85 ± 0.11, indicating competitive inhibition. While secretin also stimulated AC activity, although 1,000-fold less potent than VIP, glucagon was ineffective. These data indicate that specific VIP receptors, which mediate VIP-stimulated bicarbonate secretion, are present on villous enterocytes. Stimulation of AC by secretin seems to be of pharmacological relevance only and is consistent with the lack of effect of this hormone on DBS. Glucagon likely activates a second transmitter of bicarbonate secretion

ISSN:0031-7012    

DOI:10.1159/000139400

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Potassium channel openers are currently being evaluated for their inhibitory effect on hyperreflexia. Increasing potassium permeability results in a hyperpolarization of the smooth muscle membrane and a reduction in calcium entry. This stabilizes the membrane and should result in the reduction of spontaneous contractile activity. Potassium channel agonists have been shown to be effective in the reduction of hyperreflexia secondary to outlet obstruction in rats, and certainly have been shown to reduce the contractile responses of isolated tissues to a number of different agonists. In addition, intravesical administration of potassium channel openers have been shown to be effective against hyperreflexia (in rabbits) using intravesical administration, although relatively high concentrations had to be employed. Using an in vitro whole bladder model (rat), our current study compares the potency and efficacy of intravesical versus extravesical administration of two potassium channel openers for the inhibition of field-stimulated contraction. The results demonstrate that (1) the extracellular administration of ZD6169 and cromakalim were equally effective inhibitors of the contractile response to field stimulation, (2) low frequency stimulation was inhibited to a significantly greater degree than high frequency stimulation, (3) intravesical administration of ZD6169 was equally effective at inhibiting the response to low frequency field stimulation when compared to extravesical administration, (4) intravesical administration was less effective than extravesical administration at high frequency stimulation (although the inhibition was still statistically significant), and (5) intravesical administration of cromakalim did not inhibit field stimulation.

ISSN:0031-7012    

DOI:10.1159/000139401

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We examined the effects of subarachnoid hemorrhage (SAH) and treatment with deferoxamine (DFO) or sympathectomy on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording the responses to nor-adrenaline and serotonin in isolated carotid arteries in vitro. All studies were performed before and 7 days after SAH. An experimental subarachnoid hemorrhage model was created in rabbits by injecting autologous arterial blood into the subarachnoid space of the rabbits via cisterna magna punction. During the chronic stage of vasospasm following SAH deferoxamine (DFO) was given to the animals and cervical and periarterial sympathectomy was performed in the other groups of animals. In isolated carotid arteries noradrenaline (10–8 to 10–4 mol/l) and serotonin (10–8 to 10–4 mol/l) produced concentration-dependent contractions. These contractile responses were significantly enhanced in animals 7 days after SAH compared to controls and did not return to control values in carotid arteries obtained from animals treated with DFO or sympathectomy for 7 days after SAH. These results show that SAH causes supersensitivity in the carotid as well as cerebral arteries during the first week after SAH and could contribute to the development of cerebral vasospasm. Both treatment with DFO and sympathectomy after SAH did not reduce the contractile responses to noradrenaline and serotonin in the carotid arteries. In conclusion, treatment with DFO or sympathectomy during the chronic stage of vasospasm after SAH did not affect the vascular responses of the extradural part of the carotid artery to vasoactive sub

ISSN:0031-7012    

DOI:10.1159/000139402

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Protoporphyrin accumulates in tissues after administration of δ-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, δ-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after δ-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary δ-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic th

ISSN:0031-7012    

DOI:10.1159/000139403

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied the effects of diazepam, CL 218,872, Ro 15-1788, β-CCM and Ro 15-4513 on the γ-aminobutyric acid-activated current in adult and newborn rat superior cervical ganglion neurons. Diazepam (10–1,000 nmol/l) potentiated the current in a concentration-dependent manner. CL 218,872 was less effective and weaker than diazepam. The other ligands reduced the amplitude of the current. These peripheral receptors might be involved in some of the side effects of benzodiazepi

ISSN:0031-7012    

DOI:10.1159/000139404

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effect of a novel thiazole derivative, SM-8849, on experimental arthritis in mice was studied and compared to that of prednisolone. SM-8849 and prednisolone reduced the incidence and severity of type II collagen-induced arthritis in mice, as assayed by clinical observation and histopathological studies. Although both agents inhibited type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice, SM-8849 did not affect the production of humoral antibodies to type II collagen. To examine the inhibitory mechanism of SM-8849, the effects on T cell-dependent allergic inflammation were studied. SM-8849 clearly inhibited T cell-dependent reactions including staphylococcal enterotoxin B (SEB)-induced arthritis, SEB-induced CD25 expression on T cells and sheep red blood cell (SRBC)-induced DTH reaction. SM-8849, however, had no effect on the production of humoral antibody forming cells in the spleen of mice immunized with SRBC. These results indicate that inhibition of type II collagen-induced arthritis by SM-8849 is mainly due to the inactivation of T cells that are related to DTH reaction.

ISSN:0031-7012    

DOI:10.1159/000139405

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of subcutaneous pretreatment with the glucocorticoid/progesterone receptor antagonist RU 486 on the antinociceptive action of peripherally administered morphine were evaluated by the hot-plate test in mice. The steroid significantly reduced the analgesic effect of the opiate. Neither dexamethasone nor progesterone modified the effects of RU 486 on morphine-induced analgesia. Therefore, the present data indicate that the modulatory effect of RU 486 on morphine-induced analgesia does not involve the binding of this drug to classical steroid receptors.

ISSN:0031-7012    

DOI:10.1159/000139406

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139407

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139408

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139399

出版商:S. Karger AG    

年代:1996

数据来源: Karger