Exocrine ductalpCO2 in the rabbit pancreas

An improvedpCO₂ microelectrode has been evaluated and used to investigate whether a significant barrier to diffusion of CO₂ exists in the rabbit pancreas. The results of this study show the improved Carter and CaflischpCO₂ microelectrode to be an accurate and reliable tool for measuring pancreatic venous and ductalpCO₂. The similarities betweenpCO₂ values from the pancreatic ducts and small pancreatic veins suggest that there is no barrier to CO₂ diffusion between small veins and exocrine ducts in the rabbit pancreas, and that ductalpCO₂ is probably strongly influenced by the CO₂ tension of the small pancreatic blood vessels.     

Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug,of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors

Summary Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxytryptamine_1A (5-HT_1A) agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 3 , 4 , 7 , 7 -hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-IH-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT_1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT_1A antagonistic activity. Direct microinjection of these 5-HTIA selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HTIA receptors. Send offprint requests to A. Hirose at the above address     

The preferential inhibition of α1- over β-adrenoceptor-mediated positive inotropic effect by organic calcium antagonists in the rabbit papillary muscle

Summary Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by ₁-adrenoceptors is more susceptible to organic calcium antagonists than the -adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [³H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via _l-adrenoceptors in ₁- concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [³H]prazosin binding and to inhibit the -mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the al-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by -adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the - and -mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the ₁-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of -mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca²⁺ subsequent to ₁-and -adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart. Send offprint requests to M. Endoh at the above address     

Analysis of the actions of 5-hydroxytryptamine on the rabbit isolated vagus nerve

Summary Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1–100 mol/l) was applied either as single concentrations or cumulatively and EC₅₀ and IC₅₀ values measured from individual concentration-response curves. The EC₅₀ values for depolarization (cumulative curves: 2.33, 1.64–3.33 mol/l, geometric means and 95% confidence limits, n = 31; non-cumulative curves: 3.99, 2.89 – 5.52 mol/l, n = 9) were significantly higher than IC₅₀ values for C spike reduction (cumulative curves: 1.25, 0.91–1.74 mol/l, n = 30; non-cumulative curves: 1.41, 0.72–2.76 mol/l, n = 8). Complex effects on the C spike were observed, suggesting a susceptible group of C fibres and a 5-HT-resistant component to the C fibre action potential. The motor nerve C fibres in the vagus nerve appear insensitive to 5-HT, whereas the sensory C fibres were sensitive to 5-HT. Phenylbiguanide had a similar selective effect on the C spike, while the depolarizing agents, 1,1-dimethyl-4-phenylpiperazinium (DMPP) and gamma-aminobutyric acid (GABA) did not. Cumulative concentration-response curves for depolarization and C spike reduction could be repeated reproducibly if an interval of 90 min was left between determinations. Up to 6 curves could be generated from one preparation. The 5-HT uptake inhibitor, citalopram (0.1 and 1 mol/l), had no effect on cumulative concentration-response curves. Concentration-response curves from pooled data, when 5-HT was applied non-cumulatively, showed higher maxima for both depolarization and C spike reduction compared to similar curves for cumulative application of increasing concentrations of 5-HT. It is concluded that although the two actions of 5-HT on the rabbit vagus nerve (depolarization, C spike reduction) closely parallel each other in respect of their cumulative and non-cumulative concentration-response curves, the repeatability of concentration-response curves, and, as reported in a companion paper, blockade by metoclopramide or BRL 43694 and involvement of 5-HT₃ receptors, some differences remain which may or may not indicate an independent genesis of the two responses.Send offprint requests to D. I. Wallis at the above address     

Evidence for two separate vasoconstriction-mediating nucleotide receptors,both distinct from the P2X-receptor,in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides

Summary Uridine 5-triphosphate- (UTP-) and adenosine 5-triphosphate-(ATP) induced vasoconstriction was studied in the rabbit basilar artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure.Serotonin, histamine and noradrenaline caused concentration-dependent vasoconstriction, with potency decreasing in that order. Of the nucleotides tested, UTP, UDP, UMP, CTP, ATP, ADP, adenosine 5-O-(3-thio)triphosphate (ATPS), and ,-imido adenosine 5-triphosphate (AMP-PNP) elicited concentration-dependent vasoconstriction, whereas AMP, 2-methylthio-ATP, , -methylene-ATP and ,-methylene-ATP up to 10^–3 mol/l caused no or only a very small increase in perfusion pressure. The order of potency of the pyrimidine nucleotides was: UTP = UDP UMP = CTP; that of the purine nucleotides was: ATPS > AMP-PNP > ATP > ADP > 2-methylthio-ATP = , -methylene-ATP = ,-methylene-ATP. The vasoconstrictor effects of UTP and ATP were not or only to a minor degree influenced by: phentolamine; a mixture of atropine, diphenhydramine and methysergide; indometacin; nordihydroguaiaretic acid; denervation by 6-hydroxydopamine; or mechanical removal of endothelium. Prolonged exposure to ,-methylene-ATP elicited only a very small vasoconstriction and did not change the constrictor effects of UTP or ATP. Prolonged exposure to ATPS elicited marked vasoconstriction; subsequently, responses to ATP were reduced whereas those to UTP were, if anything, slightly enhanced. Reactive blue 2 reduced neither the UTP- nor the ATP-induced vasoconstriction. ATP 10^–3 mol/l elicited marked additional vasoconstriction after precontraction with UTP 10^–3 mol/l, whereas UTP elicited only a very small additional vasoconstriction when its concentration was doubled from 10^–3 to 2 × 10^–3 mol/l.It is concluded that, in the rabbit basilar artery, the vasoconstrictor response to UTP is mediated by a pyrimidine nucleotide receptor which is distinct from the P₂-purinoceptor, and that the vasoconstrictor response to ATP is mediated by a P₂-receptor which is distinct from the known P₂-subtypes.Send offprint requests to I. v. Kügelgen at the above address     

Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. 1. Biochemical and clinical effects

The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 g/kg body weight and the high-dose group (15 animals) 0.80–1.20 g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 g/l after 70 days and in the high-dose group to ca. 900 g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 g lead/l blood no adverse effects were observed that did occur at the high dose level.Part 2, dealing with the histopathology and (electron) microscopy of the kidneys is in preparation     

经皮肺内注射无水乙醇的动物实验研究

为了观察经皮穿刺注射无水乙醇对肺组织的局部作用和全身影响 ,为经皮穿刺注射无水乙醇 (PEI)治疗肺癌的安全性和可行性提供依据 ,我们进行了家兔肺内PEI的初步实验研究。结果显示 :PEI后的第 1天至第 3天 ,注射局部的肺组织发生凝固性坏死 ,周围肺水肿、充血 ,伴大量嗜中性白细胞浸润。 1～ 2周后 ,肺局灶性上皮细胞肉芽组织增生 ,最后纤维化。PEI早期既无大面积肺组织坏死 ,亦无明显的全身副作用。本研究结果提示 ,肺内PEI是安全可行的     

炭纤维细粉注入动物颅内的组织病理学和移动规律研究

目的 :研究炭纤维对动物大脑皮质神经细胞的影响及炭纤维在颅内的移动规律。方法 :将炭纤维细粉注入小鼠和家兔左侧大脑颞叶皮质内 ,动态观察脑组织病理学改变及炭纤维在颅内的移动。结果 :实验组 (EG)术后 1～ 5 2周 ,未发现小鼠和家兔有与炭纤维注入有关的神经病学改变 ;术后 1～ 2周 ,EG与 CG(对照组 )小鼠和家兔的脑组织病理学检查显示轻度异常改变 ,二组间差异不显著 ;术后 4～ 5 2周 ,EG、CG小鼠和家兔的脑组织未见明显的损伤性病变 ,EG可见炭纤维向脑内的正常裂隙移动和沉积。结论 :1炭纤维细粉注入动物大脑颞叶皮质后显示出良好的组织相容性 ;2注入动物脑内的炭纤维细粉崩解形成的碎屑最终可能通过淋巴途径清除。     

肝性脂酶及脂蛋白脂酶在兔胆囊结石形成过程中的变化及意义

为研究肝脂酶及脂蛋白脂酶在胆固醇结石成石过程中的变化及其对成石的影响,采用高胆固醇膳食诱发兔胆囊胆固醇结石模型,观测对照组及高胆固醇膳食1、2 、3、4周组动物血浆脂蛋白脂酶(LPL)、肝脂酶(HL)活性、血浆脂蛋白胆固醇及胆汁中甘氨胆酸(GCA)、甘氨脱氧胆酸(GDCA)、胆固醇的变化.结果显示:随着进食高胆固醇膳食时间的增加,血中LPL活性增高明显(P＜0.05);HL活性也逐渐升高,3周组及4 周组与对照组差异显著(P＜0.05);血中VLDL-C、LDL-C及胆汁中胆固醇也明显升高(P ＜0.05);而血中 HDL-C、HDL2-C及HDL3-C以及胆汁中GCA、GDCA无明显变化(P＞0.05).结果表明:LPL及HL活性升高可能使肝脏摄取及向胆汁中排泌胆固醇增加,进而影响结石形成.