β-N-acetylglucosaminidase and β-glucuronidase activities in insulin-dependent diabetic subjects with retinopathy

Summary The serum activities of two lysosomal enzymes, -N-acetylglucosaminidase (EC 3.2.1.30, NAG) and -glucuronidase (EC 3.2.1.31, GLU), were determined in 41 insulin-dependent diabetics, 27 age-matched non-diabetic first-degree relatives of the diabetics and 103 age-matched non-diabetic blood-donors. The diabetics were divided into three groups on the basis of ophthalmoscopy: (1) no retinal abnormalities; (2) non-proliferative retinopathy; and (3) proliferative retinopathy. The activities of both serum enzymes were higher in diabetics (NAG 21.39 ±5.99; GLU 2.19±1.01) than in their relatives (NAG 17.22±3.99; GLU 1.62±0.61). The diabetics with non-proliferative retinopathy had higher serum enzyme levels (NAG 24.05±6.26; GLU 2.60 ±1.06) than diabetics without retinopathy (NAG 17.88±3.00; GLU 1.69±0.64), whereas no statistically significant difference was found in patients with the proliferative form of retinopathy (NAG 18.67±6.28; GLU 1.99±1.04). In diabetics a positive correlation was found between serum -N-acetylglucosaminidase activity and blood glucose (p < 0.01), but not between -glucuronidase and blood glucose. Furthermore, the activities of both enzymes in diabetics correlated with the plasma triglyceride level (p<0.05 for both correlations). No correlation was found between the enzyme levels and signs of other diabetic late complications.     

Macrophages enhance binding of beta-VLDL and cholesterol ester accumulation in cultured aortic smooth muscle cells

Summary The effect of macrophages on the uptake of -very low-density lipoprotein (-VLDL) by smooth muscle cells (SMC) expressing different morphological phenotypes was examined in culture. The SMC were grown alone and in co-culture with macrophages for four days, then incubated with different concentrations of¹²⁵I--VLDL for 3 h at 4°C or with 75 ug/ml -VLDL for 24h at 37°C. The binding of -VLDL to SMC at 4°C was enhanced in the presence of macrophages irrespective of the phenotype expressed by SMC. This occurred through modification of the lipoprotein, since binding of re-isolated macrophage-conditioned -VLDL to SMC was 12.5 times that of fresh -VLDL. This modified form of -VLDL competed with fresh -VLDL for binding to SMC. Binding was inhibited in the presence of probucol, suggesting that an oxidative mechanism may be involved.The presence of macrophages also enhanced the accumulation of -VLDL-derived cholesterol in SMC. While most of this is a consequence of the enhanced binding, macrophages may also act directly on SMC to increase cholesterol accumulation, since the activity of acid cholesterol ester hydrolase and neutral cholesterol ester hydrolase in SMC was reduced in the presence of macrophages.     

The insulin response to glucose infusion in gestational diabetes

Summary Using a glucose infusion test insulin responses and insulin sensitivities were studied in 15 gestational diabetic women at 36–40 weeks gestation. In all women intravenous glucose tolerance had returned to normal at six weeks postpartum. Twelve women had a repeat glucose infusion test done 7–24 weeks (mean 17 weeks) postpartum. The results were compared with previously evaluated normal non-pregnant and normal pregnant standards and insulin responses below the normal 15^th percentile were defined as low. Twelve women had low insulin responses in late pregnancy, and six had low insulin responses postpartum. The mean insulin sensitivity index of 1.34±1.21 (mean ±SD) was significantly higher in the gestational diabetic group during pregnancy compared with a control pregnant group at 0.53±0.21 (p<0.01). The findings in this study support the hypothesis that gestational diabetes may arise in women who are unable to achieve adequate insulinogenic compensation to pregnancy. Increased insulin sensitivity in gestational diabetes may be a compensatory mechanism.     

Interactive influences of peroxisome proliferator-activated receptor α activation and glucocorticoids on pancreatic beta cell compensation in insulin resistance induced by dietary saturated fat in the rat

Aims/hypothesis We sought to elucidate whether excess glucocorticoids and increased dietary lipids act synergistically to impair glucose tolerance and, if so, whether activation of peroxisome proliferator-activated receptor (PPAR) has an adverse or beneficial effect on glucose tolerance.Methods Dexamethasone (100 g kg^–1 body weight day^–1; 5 days) was administered to insulin-resistant rats fed a high-saturated-fat (HF) diet for 4weeks. The PPAR agonist WY14643 was administered (50 mg kg^–1 body weight intraperitoneally) 24 h before sampling. Glucose-stimulated insulin secretion (GSIS) was assessed in vivo after an acute glucose bolus injection, and in vitro using step-up and step-down islet perifusions.Results Although neither PPAR activation nor dexamethasone alone affected fasting glycaemia in the HF group, dexamethasone in combination with PPAR activation elicited marked postabsorptive hyperglycaemia. Dexamethasone treatment of HF rats had little effect on GSIS after an acute glucose challenge in vivo, but induced glucose intolerance. PPAR activation augmented GSIS in dexamethasone-treated HF rats in vivo, restoring glucose tolerance. Contrasting with data obtained in vivo, greatly enhanced peak rates of GSIS were observed ex vivo in perifusions of islets from dexamethasone-treated HF rats compared with those from untreated HF rats, an effect attenuated by antecedent PPAR activation.Conclusions/interpretation The study demonstrates that glucocorticoid excess precipitates the development of glucose intolerance in rats maintained on a high-saturated-fat diet. It does this by interrupting the negative feedback loop between insulin sensitivity and secretion in vivo, such that further enhancement of compensatory insulin secretion is not possible. PPAR activation restores the coupling between insulin secretion and action.     

Bone marrow and peripheral blood globin chain biosynthesis in iron deficiency

Summary Globin chain synthesis was studied in 13 iron-deficient patients. The mean whole-cell globin / ratio in the peripheral blood of 11 patients was 1.05±0.06 which is similar to the value 0.99±0.08 obtained for 10 controls. The ratios odtained for stroma-free globin were not significantly different from those of whole cell preparations. In contrast, the / ratio of bone marrow was 0.73±0.14 in 10 iron deficient patients, which is significantly lower than that of controls. Two other patients had decreased / ratios in the peripheral blood, probably because of the presence of an -thalassemia gene. These results demonstrate a reduced rate of synthesis of chains relative to that of chains in the bone marrow of iron-deficient patients that is not demonstrable in the peripheral blood.This work was partly supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.     

Effect of gold therapy on CD5+ B-cells and TCR γδ + T-cells in patients with rheumatoid arthritis

Summary Circulating CD5⁺ B-cell levels in 15 patients with rheumatoid arthritis (RA) not receiving remittive therapy was significantly increased when compared to 17 normal controls (mean±SE: RA, 19.7±2.85%; controls, 11.6±1.67%; P<0.02). In contrast, 24 patients with RA receiving gold sodium thiomalate therapy (GST) had similar CD5⁺ B-cell levels (11.88±1.65) when compared to controls and significantly reduced levels when compared to the RA group not receiving remittive agents (P<0.01). Furthermore, TCR ⁺ T-cell levels were also assessed in these patients groups. These values were not significantly different between any of the groups (controls, 4.46±1.36%; GST, 6.88±1.73%; RA, 2.73±0.55%), although 42% of the GST treated group had ⁺ T-cell levels higher than the entire untreated RA group. No correlation was observed between the levels of TCR ⁺ T-cells and CD5⁺ B-cells in any of these groups. These results suggested that therapy does influence the level of CD5⁺ B-cells and ⁺ T-cells in these patients.     

Compound heterozygosity for a β∘-thalassemia (frameshift codons 38/39; -C) and a nondeletional swiss type of HPFH (A→C at NT -110, Gγ) in a Czechoslovakian family

Summary We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered -thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an AC mutation at nucleotide –100 5 to the Cap site of G), or with a compound heterozygosity for these two conditions. The Hb F level in the -thalassemia heterozygotes averaged 0.3% with low G values ( 28%) and relatively high AT values ( 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with 95% G, while that of the compound heterozygote was 3.1% with 95% G. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%–0.2% Hb F level [3]. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.This study was supported in part by USPHS Research Grant HLB-41544     

Acetaldehyde accumulation suppresses Kupffer cell release of TNF-Α and modifies acute hepatic inflammation in rats

Background Alcohol-related diseases have multiple and varied associations with acetaldehyde, a highly toxic product of ethanol oxidation that accumulates in the absence of active aldehyde dehydrogenase (ALDH). This study was designed to clarify the role of acetaldehyde in liver injury, specifically in vivo and in vitro effects on Kupffer cell release of the inflammatory cytokine tumor necrosis factor-alpha (TNF-).Methods Rats pretreated overnight with the ALDH inhibitor disulfiram (or saline control) were ethanol loaded and challenged with lipopolysaccharide (LPS), and their blood and histological parameters were examined 3h later. Similarly, isolated rat Kupffer cells were pretreated with disulfiram or cyanamide incubated in ethanol (1h), then challenged with LPS and evaluated 2h later for TNF- and acetaldehyde levels in the culture medium. TNF- release from Kupffer cells after LPS challenge was also evaluated following incubation in acetaldehyde and acetate for comparison with ethanol loading.Results Higher blood acetaldehyde concentration following disulfiram pretreatment significantly attenuated acute hepatic inflammation in the ethanol-loaded, LPS-challenged rat (18 ± 2.9 vs 30 ± 3.7 polymorphonuclear cells/portal area; P = 0.01). After LPS challenge, ALDH inhibitor pretreatment attenuated Kupffer cell release of TNF- in the presence of disulfiram at 5063 ± 151pg/ml and cyanamide at 4390 ± 934pg/ml, versus no inhibitor, 5869 ± 265pg/ml (P 0.01), but not in the absence of ethanol. Acetaldehyde significantly suppressed Kupffer cell TNF- release (P 0.05), but acetate treatment did not.Conclusions Acetaldehyde accumulation suppresses macrophage function, at least suppressing TNF- release, which plays a role in modifying acute hepatic inflammation in rats.     

Distribution of β-Adrenoceptor Subtypes in Gastrointestinal Tract of Nondiabetic and Diabetic BB Rats A Longitudinal Study

The effects of aging and diabetes on thedistribution of -adrenoceptor subtypes in the gutwere investigated in the BB rat.[¹²⁵I]Cyanopindolol binding to 10-msections was evaluated using film autoradiography. Cyanopindolol binding to -,₁-, and₂-adrenoceptors was displaced by 1M propranolol, 50 nM ICI-89-406, and 100 nMICI-118-551, respectively. -Adrenoceptor bindingwas highest in the circular muscle of proximal colon and lowest in thepylorus of 4- to 5-month-old rats. Aging (8- to10-month-old vs. 4- to 5-month-old rats) was associatedwith increased -adrenoceptor binding in thepylorus and reduced binding in the proximal colon.Diabetes had a time-dependent effect on the level of-adrenoceptor binding. It was increased in theantral and pyloric stomach but longer periods ofdiabetes caused a reduction in -adrenoceptorbinding in the pylorus. Those in the intestine werereduced time-dependently and involved₁- or ₂-adrenoceptorsor both.     

Different effects of glucose and glyburide on insulin secretion in rat pancreatic islets pre-exposed to interleukin-1β. Possible involvement of K+ and Ca2+ channels

Summary In vitro islet exposure to interleukin 1 inhibits the beta-cell response to glucose. We have studied whether a similar inhibition also occurs in response to the sulphonylurea glyburide. Rat pancreatic islets were cultured for 24 h in the presence or absence of 50 U/ml interleukin 1 and then stimulated with either glucose or glyburide for 1 h at 37 °C. In control islets basal insulin secretion was 117±32 pg · islet^–1 · h^–1 (mean ± SEM, n=7) and greatly increased in response to 16.7 mmol/l glucose (2140±293) or 10 mol/l glyburide (1464±234). When islets were pre-exposed to interleukin 1, insulin release was significantly reduced in response to glucose (323±80, p<0.001) but not in response to glyburide (1316±185). Since both glucose and glyburide influence beta-cell K⁺ and Ca²⁺ efflux, to further investigate this different response in islets exposed to interleukin 1 we measured both Rb⁺ efflux (as index of the ATP-sensitive K⁺ channel activity) and Ca²⁺ uptake. In control islets, the increased insulin secretion in response to 16.7 mmol/l glucose or 10 mol/l glyburide was associated with a reduction of ⁸⁶Rb efflux (decrement of –50±1.2 % and –49±2.3 %, respectively, mean ± SEM, n=5). In contrast, in interleukin 1pre-exposed islets both glucose and glyburide stimulation only slightly modified ⁸⁶Rb efflux (decrement of –19±1.9% and –5.3±3.1 %, respectively, n=5, p<0.001). ⁴⁵Ca²⁺ uptake in control islets was 2.6±0.4 pmol · islet^–1 · 20 min^–1 under basal conditions (at 2.8 mmol/l glucose), and increased to 16.8±3.2 and 10.7±2.1 pmol · islet^–1 · 20 min^–1 in islets stimulated with 16.7 mmol/l glucose or 10 mol/l glyburide, respectively (mean ± SEM, n=6). ⁴⁵Ca²⁺ uptake in interleukin 1 treated islets was higher than in control islets under basal conditions (4.6±0.6 pmol · islet^–1 · 20 min^–1 at 2.8 mmol/l glucose, p<0.05), but was significantly reduced in response to glucose 16.7 mmol/l (7.1±1.1, p<0.01 with respect to control islets). In contrast to glucose, 10 mol/l glyburide was able to stimulate calcium uptake in interleukin 1 treated islets in a similar way to control islets (12.8±2.5). The present data demonstrate that rat pancreatic islets treated with interleukin 1 for 24 h lose their responsivity to glucose, but not to glyburide. The difference between the two secretagogues is associated with the persistent ability of glyburide to influence Ca²⁺ uptake even in islets with impaired K⁺-channel function.     

Serum cytokines in patients with rheumatoid arthritis

Serum cytokines such as interleukin 1 (IL-1), interferon (IFN-), and tumor necrosis factor (TNF) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1 was detected in 5 patients, IFN- in 10 patients, and TNF in 20 patients. The IL-1-positive group showed increased values of activity indices compared to the IL-1-negative group. Values of serum IFN- correlated well with the number of peripheral blood lymphocytes and CD3⁺ cells and with the percentage of CD3⁺ CD26⁺ cells. Values of serum TNF correlated positively with the number of peripheral blood monocytes and the percentage of CD3⁺ HLA-DR⁺ and CD3⁺ CD25⁺ cells. These results indicated that serum IL-1 in RA patients reflects the activity of RA, while the serum IFN- and TNF in RA patients may be related to circulating activated lymphocytes and monocytes, respectively.     

The effects of parabiosis on serum and kidney glycosidase activities in spontaneously diabetic mice

Summary Spontaneously diabetic non-obese mice of the ICR strain were newly inbred in Shionogi laboratory, Japan. Animals became diabetic suddenly, more frequently and severely in females. Blood glucose levels were 452±73 mg/100 ml with serum insulin levels of < 1.0 U/ml in the fed state. Parabiosis with normal control ICR mice for 2 weeks decreased the blood glucose level to 260±51 mg/ 100ml (P<0.01) and resulted in serum insulin levels of 46.0±18.0 U/ml (P<0.01). Kidney homogenate -N-acetylglucosaminidase and -galactosidase activities were reduced in diabetic mice (42% and 44% decrease respectively) (P<0.025 and P<0.001), and restored almost to normal after 2 weeks of parabiosis. Renal -mannosidase activity was decreased 43% (P<0.001) in the diabetic mice but unaffected by parabiosis. Serum -N-acetylglucosaminidase, -galactosidase and -glucosidase activities were significantly increased in diabetic mice (179%; 233% and 58% increase respectively) (P<0.005, P<0.001 and P<0.001), and returned to normal with parabiosis.     

“Mini-perforation” of the colon—Not all postpolypectomy perforations require laparotomy

In a 10-year experience with 4,784 consecutive colonoscopic polypectomies, the need for operative intervention in just two of seven perforations indicates that patients with specially defined, limited perforations can usually be treated nonoperatively. This specific complication, which has been termed mini-perforation, is generally detected within 6–24 hours of polypectomy, and is characterized by local pain and tenderness, without signs of diffuse or spreading peritoneal irritation. Free intra-abdominal or retroperitoneal air on x-ray documents the actual perforation. Complete resolution of symptoms within 24–48 hours confirms the diagnosis of mini-perforation. Success depends on good bowel preparation for colonoscopy, and early recognition of perforation, with institution of bowel rest and intravenous antibiotics. The mini-perforation spontaneously closes, probably by omental adherence. Frequent serial clinical examinations are mandatory so that frank perforation with advancing peritonitis will be promptly recognized and treated surgically. An understanding of the three levels of cautery injury to the colon wall—serosal burn, mini-perforation, and frank perforation are essential in managing the complications of colonoscopic polypectomy.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29–May 4, 1990.     

Hyperplasia of “pancreatic polypeptide”-cells in the pancreas of juvenile diabetics

Summary The cellular composition of the pancreatic islets of juvenile diabetics was studied, using recently developed immunocytochemical methods. B-cells were identified only in juvenile diabetics with a disease of short duration. In chronic juvenile diabetics, the islets which are classically viewed as atrophic, were shown to be composed of glucagon- and of somatostatin-cells. Another type of islets which commonly occurs in the pancreas of juvenile diabetics, i. e. the ribbon-like type first described by Cecil in 1911, appeared to be composed almost exclusively of pancreatic polypeptide (HPP)-cells. It is suggested that hyperplasia of the HPP-cells in the pancreas of juvenile diabetics results from an atypical type of islet regeneration induced by a severe and prolonged injury to the pancreatic endocrine tissue.     

β-Endorphin-like immunoreactivity in normal mucosa,muscle layer,adenocarcinoma, and polyp of the colon

-Endorphin-like immunoreactivity was detected in the mucosa and muscle layer of normal colon, adenocarcinomas derived from the colon mucosa, and colon polyps which were histologically confirmed to be adenoma without a focus of carcinoma or with in situ carcinoma. The contents of -endorphin-like immunoreactivity in adenocarcinomatous tissue (11.94± 1.77 pmollg wet wt) and colon polyps without focus of carcinoma (10.71 ±1.50 pmollg wet wt) were found to be significantly higher than those in the mucosal layer (6.86± 0.64 pmollg wet wt) and muscle layer (8.30 ±0.68 pmollg wet wt) of normal colon. These data suggest that the production of -endorphin-like immunoreactivity is specifically increased in some adenocarcinomas and adenomatous polyps and may be related to the alteration of bowel habits. Gel exclusion chromatography of - endorphinlike immunoreactivity revealed three peaks corresponding to -endorphin, -lipotropin, and an immunoreactive form between the two. In the mucosal layer and muscle layer of the colon, a broad major peak was eluted at the position of -endorphin, and minor peaks were eluted at the position of -lipotropin and between -endorphin and -lipotropin. In adenocarcinoma and polyp, the peak size corresponding to authentic -lipotropin was greater than that of -endorphin. This study demonstrated that -endorphin-like immunoreactivity existed at a high concentration in some colon adenocarcinomas and polyps whose elution patterns were different from those of normal colon tissue.     

Lack of α2-Antiplasmin Enhances ADP Induced Platelet Micro-Aggregation through the Presence of Excess Active Plasmin in Mice

Background: The role of 2-antiplasmin (2-AP) on platelet aggregation was investigated using mice deficient in 2-AP (2-AP^–/–) or using wild type mice (2-AP^+/+). Methods: Blood samples were taken from each mouse under anesthesia with ether and platelet rich plasma (PRP) was prepared. Platelet aggregation induced by various doses of ADP (0.3–30 M) was detected using a laser-light scattering (LS) system. Aggregated forms were observed using a scanning electron microscopy (SEM). Results: Dose-dependent platelet aggregation was not different in both types of mice. However, platelet micro-aggregate formation in 2-AP^–/– mice induced by low dose of ADP (1.0 M) markedly increased compared to the situation in wild type mice. Aggregated form detected by SEM showed supported data from LS analysis. When washed platelets of 2-AP^+/+ mice were resuspended in plasma of 2-AP^–/– mice, platelet micro-aggregation was also increased. On the contrary, when washed platelets of 2-AP^–/– mice were suspended in plasma of 2-AP^+/+ mice, platelet micro-aggregation did not change. In separate experiments, tPA (1.0 g/ml) was added to PRP before the stimulation of ADP. tPA had no effect on platelet aggregation in 2-AP^+/+ mice, however platelet micro-aggregation in 2-AP^–/– mice was markedly increased by the treatment with tPA. Moreover, the amount of released ATP from stimulated platelets was increased in 2-AP^–/– mice treated with tPA. Conclusion: Lack of 2-AP increased platelet micro-aggregation, and plasmin plays an important role in the formation of platelet aggregation when 2-AP knockout mice are used. Consequently, the reduction of 2-AP could be a risk factor for the activation of platelets resulting in thrombus formation.     

Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons,sensory neuropeptides,and prostaglandins

The mechanisms by which transforming growth factor- (TGF-) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGF gastroprotection against ethanol. Fasted rats received TGF- (50 g/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF--mediated gastroprotection. TGF- significantly diminished ethanol-induced gastric lesion area to 5.7 ± 0.8 mm² vs 4l.1 ± 5.2 mm² (P < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF- protective effect. In contrast, SP antagonist and indomethacin did not alter TGF- gastroprotection. In conclusion, TGF--mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.     

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.     

Effects of bile salts on plasma concentration of β-endorphin-like immunoreactivity in men

The effects of bile salts on the release of -endorphin-like immunoreactivity ( -END-LI) were investigated in men using a specific radioimmunoassay developed by the authors. Plasma -END-LI was determined after extraction by the acid-acetone method (recovery: 73±5%). Oral administration of 400 mg of sodium taurocholate caused a rise in plasma -END-LI from 9.9±0.5 pmol/liter to 21.3±1.2 pmol/liter after 30 min and 18.1 ±0.5 pmol/liter after 60 min, with return to the initial value after 90 min. Oral administration of chenodeoxycholic acid (CDCA) also increased plasma -END-LI from a basal level of 8.4±0.7 pmol/liter to 18.7±0.8 pmol/liter after 30 min. Oral administration of ursodeoxycholic acid (UDCA) increased plasma -END-LI from 7.3±0.3 pmol/liter to 30.6±0.2 pmol/liter after 30 min. In gel chromatography, the -END-LI released after UDCA administration separated into two components, which eluted in the same positions as human -lipotropin and human -endorphin, respectively. These results suggested that bile salts may participate the release of -END-LI.