Beta-adrenoreceptors in the muscular tissue of Anodonta cygnea

The beta-adrenoceptors in the muscular tissue of Anodonta cygnea have been studied for the first time with the use of antagonist [125I] iodocyanopindolol. The tissue membrane had only one class of binding sites with Kd 2.9 +/- 0.02 pM and the maximal number of binding sites (Bmax) 110 +/- 2.4 fmoles/mg of protein. The potency of beta-agonists and antagonists for displacing [125I] iodocyanopindolol for its beta-AR complexes was the following: isoproterenol greater than adrenaline greater than noradrenaline-propranolol greater than serotonin much greater than dopamine greater than phentolamine. The GTP negative regulation of beta-AR affinity has been found. The data obtained show that the beta-AR are functionally coupled with GTP-binding protein which were similar to GTP-proteins of vertebrates.     

Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex

The effect of acute treatment with seven atypical antipsychotic drugs and four typical antipsychotic drugs on serotonin2 (5-HT2) receptor binding sites in rat cerebral cortex was studied. Among the atypical antipsychotic drugs examined, clozapine, fluperlapine, RMI-81582 and setoperone decreased the density of 5-HT2 receptors, but ticspirone, amperozide and melperone did not. None of the drugs affected the Kd value. Among the typical antipsychotic drugs, loxapine decreased Bmax and increased the Kd of 5-HT2 receptor binding sites, whereas chlorpromazine and cis-flupenthixol had no effect. Clothiapine, a typical antipsychotic drug of the same chemical class as clozapine, decreased Bmax without increasing Kd. The downregulation of 5-HT2 receptor binding sites following a single injection of clozapine, 20 mg/kg, remained almost unchanged during the first 72 hrs and was still significantly decreased for up to 120 hrs. There was no relationship between the affinity for the downregulation of rat cortical 5-HT2 receptor binding site and 5-HT2 receptor density. Coadministration of the D1 dopamine agonist, SKF-38393, did not affect the clozapine-induced downregulation. It is suggested that rapid and prolonged downregulation of 5-HT2 receptor sites is characteristic of some but not all atypical antipsychotic drugs and is not specific to atypical antipsychotic drugs. Dibenzo-epines (clozapine, loxapine, amoxapine, chlothiapine) consistently downregulate 5-HT2 receptors in frontal cortex after acute treatment.     

Are there ventricle-specific postnatal maturational differences in myocardial beta-adrenoceptors?

Newborn hearts have restricted functional reserve and variable responsiveness to inotropes that could be partly due to differences in myocardial beta-adrenoceptors (beta-AR). To clarify this issue, this study documented ventricle-specific changes in myocardial beta-AR density and affinity during postnatal maturation. In vivo left and right ventricle (LV and RV, respectively) biopsies were obtained from newborn (3-day-old, n = 11), immature (14-day-old, n = 7), and adult (n = 6) pigs. Total beta-AR density (B(max), fmol/g) and dissociation constant (K(d), pmol/L) were determined by radioligand binding with I125 iodocyanopindolol. Overall, beta-AR B(max) in the LV significantly decreased with maturation. Interestingly, newborn animal hearts (LV and RV) subdivided into 2 groups: an adult-like low K(d) group with low B(max) and a fetal-like high K(d) group with high B(max), which were significantly different from one another. The high K(d) newborn group also had significantly higher K(d) and B(max) than both immature and adult hearts. Newborns had similar Bmax but higher Kd in the LV than the RV, whereas immature and adult hearts did not have ventricular differences. During maturation, beta-AR density decreased, whereas LV beta-AR binding affinity increased. Variable beta-AR maturity was also identified immediately post partum, which could potentially explain the newborn heart's variable responsiveness to inotropes. The subset of newborn hearts with lower binding affinity (reduced responsiveness) could also contribute to the newborn heart's overall reduction in functional reserve.     

Effect of topical application of estradiol-17 beta and PGE2 on PGE-binding sites in the porcine endometrium.

High- and low-affinity prostaglandin E2 (PGE2) binding sites were found on day 15 after estrus in the endometrium of cycling (Cy) and pregnant (Pr) gilts as well as gilts treated with intra-uterine Silastic beads containing estradiol-17 beta (E2) alone or in combination with PGE2 (E and PG gilts respectively) and inserted into the uterine lumen on day 10 of the cycle. The average apparent dissociation constants (Kd) and binding site concentrations (Bmax) for the high- and low-affinity sites were respectively (mean +/- SEM): 8.4 +/- 0.7 pM and 3.28 +/- 0.38 fmol/mg of protein and 5.3 +/- 0.8 nM and 71 +/- 9 fmol/mg of protein. Samples collected along the meso- and antimesometrial aspects did not differ (P greater than 0.05), although the low-affinity Bmax was higher on the antimesometrial aspect for Pr and Cy gilts only. No difference in Kd (P greater than 0.10) was found between treatments for high-affinity binding sites. For the low-affinity binding sites, Kd was higher for Pr compared to PG and E but not to Cy gilts (P less than 0.05). The high-affinity Bmax was higher (P less than 0.05) for PG, followed by E, Pr and Cy gilts (respectively: 5.50 +/- 0.26; 4.19 +/- 0.46; 1.78 +/- 0.40; 1.64 +/- 0.23 fmol/mg of protein), although Pr and Cy gilts were not different (P greater than 0.05). These results suggest that the localized presence of conceptuses in the uterus in early pregnancy does not markedly affect PGE binding sites but that intrauterine applications of Silastic beads containing E2 and PGE2 increase high-affinity Bmax and decrease low-affinity Kd.     

Administration of chlordiazepoxide affects [3H][3-MeHis2]thyrotropin-releasing hormone binding in rat brain.

The effects of acute and subchronic administration of chlordiazepoxide (CDZ) on [3H][3-methyl-histidyl2]thyrotropin-releasing hormone binding to thyrotropin-releasing hormone (TRH) receptors in membrane preparations from various regions of rat brain were examined. Acute administration of CDZ (50 mg/kg x 3 within 24 h) did not alter either the equilibrium dissociation constant (Kd) or the maximum number of binding sites (Bmax) in cerebellum (CB), olfactory bulbs (OB), frontal cortex (Cx), hypothalamus (HT) or corpus striatum (ST). However, the Kds of the pyriform cortex/amygdala (PC/A) (Kd = 3.6 +/- 0.1 nM compared to 1.9 +/- 0.1 nM in the control group; p less than 0.01) and the hippocampus (HP) (Kd = 7.8 +/- 0.7 nM compared to 2.1 +/- 0.1 nM in the control group; p less than 0.01) were increased. There were no changes in Bmax. Subchronic administration of CDZ (50 mg/kg/day for 7 days) increased the Kd of the PC/A complex (p less than 0.05), the OB (p less than 0.05) and the HP (p less than 0.01) without altering in Bmax. These results, showing regional differences in the response of TRH receptors to acute and subchronic CDZ administration, suggest that reduced affinity of TRH receptors in the PC/A complex, OB and HP may be related to some of the neurobiological actions of CDZ and/or its metabolites.     

ACTH receptors in nervous tissue. High affinity binding-sequestration of [125I]Phe2,Nle4]ACTH 1-24 in homogenates and slices from rat brain

We have demonstrated specific, high affinity binding of a biologically active Tyr23-monoiodinated derivative of ACTH, [125I][Phe2,Nle4]ACTH 1-24, in rat brain homogenates. Similarly, in metabolically inhibited and noninhibited rat whole brain slices there is a specific "binding-sequestration" process that is dependent on time, protein concentration, and pH. In homogenates, binding curves were best described by a two-site model and provided the following parameters: Kd1 = 0.65 +/- 0.47 nM, Bmax1 = 21 +/- 41 fmol/mg protein; Kd2 = 97 +/- 48 nM, Bmax2 = 3.5 +/- 1.8 pmol/mg protein. In metabolically viable brain slices, concentration-competition curves of [125I][Phe2,Nle4]ACTH 1-24 binding-sequestration can be described by three components (Kd1 = 14 +/- 24 nM, Bmax1 = 50 +/- 95 fmol/mg protein; Kd2 = 2.4 +/- 1.9 microM, Bmax2 = 44 +/- 49 pmol/mg protein; Kd3 = 0.16 +/- 1.0 mM, Bmax3 = 5.3 +/- 54 nmol/mg protein). Metabolic inhibition, by removal of glucose and addition of 100 microM ouabain, abolishes the lowest affinity, highest capacity binding-sequestrian component only (Kd1 = 7.1 +/- 14 nM, Bmax1 = 8.7 +/- 16 fmol/mg protein; Kd2 = 7.4 +/- 4.49 microM, Bmax2 = 37 +/- 27 pmol/mg protein). The two binding-sequestration parameter estimates obtained from metabolically inhibited tissue slices are not significantly different from those of the two higher affinity components obtained with noninhibited tissue. Thus, metabolic inhibition permits demonstration of ACTH receptor binding only, unconfounded by sequestration or internalization of ligand:receptor complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果观察

目的：观察不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果。方法：将90例ASAI．II级、年龄18~60岁拟行腹腔镜妇科手术的患者随机分成3组,每组30例,A组给予地佐辛0．1mg／kg开皮前15rain静脉注射;B组给予地佐辛0．15mg／kg开皮前15min静脉注射;C组给予地佐辛0．2mg／kg开皮前15min静脉注射,采用VAS评分评估术后镇痛效果并观察术后辅助镇痛药物的使用和不良反应的发生情况。结果：B、c组术后2、4、6、8h的VAS评分明显低于A组（P〈0．05）;C组术后2、4h的Ramsay评分明显高于A、B组（P〈0.05）;A组术后辅助镇痛药的使用率明显高于B组和C组（P／0．05）;3组不良反应的发生率比较均无统计学差异（P〉0．05）。结论：开皮前15rain静注地佐辛0．15mg／kg用于腹腔镜妇科手术镇痛效果好,且不增加不良反应的发生率。     

Adaptive regulation of beta-adrenergic receptors in children with insulin dependent diabetes mellitus

The beta-adrenergic receptors were investigated in partially purified mononucleal leukocytes (MNL) plasma membranes from 18 patients with IDDM in pediatric period, 9 healthy children and 8 normal adults. The decreased beta-adrenergic receptor number was seen in patients with IDDM (Bmax = 27.6 +/- 8.3 fM (125I) IHYP/mg protein) compared with normal children (Bmax = 40.4 +/- 10.4 fM (125I) IHYP/mg protein) and normal adults (Bmax = 36.9 +/- 6 fM (125I) IHYP/mg protein). MNL beta-receptor binding affinities (apparent Kd = 109.8 +/- 26.1 pM in IDDM, 102.8 +/- 46.6 pM in normal children, 130.0 +/- 43.1 pM in normal adults) did not differ. We divided the patients with IDDM into two groups based on their level of blood glycosylated hemoglobin (HbA1) when samples were taken. Group A IDDM (consisted of 9 diabetic patients with below 10% of HbA1) had markedly decreased beta-receptor numbers compared with group B IDDM (consisted of 9 diabetic patients with more than 10% of HbA1), whereas Kd was not significantly different. Also, there was negative correlation between Bmax and level of blood sugar or HbA1 in IDDM. This is the first report concerning the beta-adrenergic receptor in IDDM in pediatric period. We suggest that decreased Bmax in group B is a homeostatic response to restore the poorly-controlled hyperglycemic state to normoglycemia because the group B patients had high level of HbA1 and blood sugar.     

白芍总苷对心肌缺血再灌注大鼠内质网应激因子CHOP、GRP78、GRP94的表达及凋亡的影响

目的:研究白芍总苷(TGP)对心肌缺血再灌注(I/R)大鼠内质网应激因子CCAAT/增强子结合蛋白的同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)表达及凋亡的影响。方法:选择健康清洁级SD大鼠75只,根据随机数字表法分成5组,每组15只,分别记为假手术组、I/R组、50 mg/kg TGP组、100 mg/kg TGP组以及200 mg/kg TGP组。检测并对比各组大鼠CHOP、GRP78、GRP94水平,对比分析各组大鼠心肌I/R指标、梗死面积率以及心肌细胞的凋亡率。结果:I/R组和TGP各组的CHOP、GRP78及GRP94水平均明显高于假手术组,且TGP各组较I/R组明显更低(均P0.05)。100 mg/kg和200 mg/kg TGP组的CHOP、GRP78及GRP94水平均明显低于50 mg/kg TGP组,且200 mg/kg TGP组较100 mg/kg TGP组明显更低(均P0.05)。I/R组和TGP各组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平均明显高于假手术组,LVSP、+dp/dtmax及-dp/dtmax水平均明显低于假手术组(均P0.05)。与I/R组相比,TGP组缺血30 min的T波改变、再灌注120 min的T波改变及LVEDP水平呈剂量依赖型下降,而LVSP、+dp/dtmax及-dp/dtmax水平呈剂量依赖型上升(均P0.05)。I/R组和TGP各组的梗死面积率和心肌细胞的凋亡率均明显高于假手术组(均P0.05)。与I/R组相比,TGP组的梗死面积率和心肌细胞的凋亡率水平呈剂量依赖型下降(均P0.05)。结论:应用TGP能够明显降低MIRI大鼠内质网应激因子CHOP、GRP78、GRP94的表达,调节心肌缺血和再灌注相关标志物或临床参数的水平,显著减少心肌缺血和再灌注所致的心肌梗死面积率及细胞凋亡率。     

依托咪酯联合丙泊酚用于老年精神疾病患者行无抽搐电休克治疗的安全性分析

目的:探讨依托咪酯联合丙泊酚用于老年精神疾病患者行无抽搐电休克治疗的安全性。方法:选取我院准备进行无抽搐电休克治疗的≥60岁的老年精神疾病患者96例,随机分为依托咪酯组、丙泊酚组和依托咪酯联合丙泊酚组,每组32例。丙泊酚组予以2 mg/kg丙泊酚静注后给予改良电抽搐疗法(MECT)治疗,依托咪酯组予以0.3 mg/kg依托咪酯静注后给予改良电抽搐疗法(MECT)治疗,依托咪酯联合丙泊酚组予以依托咪酯(0.15 mg/kg)和静注丙泊酚(1 mg/kg)后予以改良电抽搐疗法(MECT)治疗。分别于麻醉诱导前、诱导中、电刺激即刻、电刺激后5分钟、10分钟检测患者的心率及血压指标。结果:与麻醉诱导前相比,三组患者麻醉诱导后HR、SBP、DBP均下降(P0.05),电刺激即刻HR、SBP、DBP均明显升高(P0.05);与电刺激即刻相比,三组患者电刺激后5 min HR、SBP、DBP显著下降(P0.05);与丙泊酚组及依托咪酯组相比,依托咪酯联合丙泊酚组麻醉诱导后HR较低,电刺激即刻HR、SBP、DBP水平较低(P0.05)。托咪酯联合丙泊酚组不良反应发生率低于依托咪酯组、丙泊酚组(P0.05)。结论:依托咪酯联合丙泊酚组在老年精神障碍患者进行无抽搐电休克治疗时的安全性较单用依托咪酯组或丙泊酚更高。     

Effect of piracetam administration on 3H-N-methylscopolamine binding in cerebral cortex of young and old rats.

Piracetam, a nootropic drug, has been used for some time in Alzheimer's disease for its facilitatory effect on learning and memory. Rats treated with piracetam (500 mg/kg, p.o.) daily, during 1 and 2 weeks, showed a significant increase in muscarinic receptor number (Bmax) and in the dissociation constant values (Kd) in the cerebral motor cortex, in binding studies using 3H-NMS as ligand. The effect was observed not only in young rats (control- Bmax = 663.4 fmol/mg protein, Kd = 0.45 nM; treated- Bmax = 961.9 fmol/mg protein, Kd = 0.82 nM) but also in aged animals (control- Bmax = 628.0 fmol/mg protein, Kd = 0.47 nM; treated-Bmax = 747.6 fmol/mg protein, Kd = 0.84 nM). Since piracetam does not interact with muscarinic receptors, the reason for its effect expressed as the enhanced number of brain muscarinic receptors is not clear but could be the result of stimulation of phospholipid synthesis and thus would represent an indirect action of the drug.     

Photoaffinity labeling of the K+-channel-associated apamin-binding molecule in smooth muscle, liver and heart membranes

High-affinity binding sites for mono[125I]iodoapamin were detected in membranes (Kd = 59 pM, Bmax = 24 fmol/mg protein) and cultured cells (Kd = 69 pM, Bmax = 2.8 fmol/mg protein) from rat heart and in membranes from guinea-pig ileum (Kd = 67 pM, Bmax 42 fmol/mg protein) and liver (Kd = 15 pM, Bmax = 43 fmol/mg protein). Binding was stimulated by K+ ions (K0.5 = 0.3-0.5 mM). Covalent labeling with arylazide [125I]iodoapamin derivatives showed that smooth muscle, liver and heart binding molecules are associated with a 85-87-kDa polypeptide. A second strongly labeled 57-kDa component was identified in liver membranes only.     

Effects of Pro-Leu-Gly-NH2 and cyclo (Leu-Gly) on the binding of 3H-quinuclidinyl benzilate to striatal cholinergic muscarinic receptors

The effects of Pro-Leu-Gly-NH2 (melanotropin release inhibiting factor, MIF) and its analog, cyclo (Leu-Gly) on the mouse and rat striatal cholinergic muscarinic receptors labeled with 3H-quinuclidinyl benzilate (QNB) were investigated. 3H-QNB bound to the rat striatal muscarinic receptors at a single high affinity site with receptor density (Bmax value) of 1200 fmol per mg protein and an apparent dissociation constant (Kd value) of 53.5 pM. At 140 pM concentration of 3H-QNB, the specific binding to the receptors was 724 fmol per mg protein. MIF in a concentration range of 10(-9) to 10(-4) M did not alter the binding of 3H-QNB but at 10(-3) M decreased the binding by 25%. Cyclo (Leu-Gly), on the other hand, in the concentration range of 10(-9) to 10(-3) M had no effect on the binding of 3H-QNB. A single injection of MIF (3 or 10 mg/kg IP) to rats did not alter the Bmax or the Kd value of 3H-QNB to bind to the striatal membranes. 3H-QNB bound to the mouse striatal muscarinic receptors at a single high affinity site with a Bmax value of 991 fmol/per mg protein and a Kd value of 21 pM. Neither acute administration of MIF (3 or 10 mg/kg IP) nor chronic treatment of the peptide (2, 8 or 32 mg/kg IP, daily for 5 days) to mice could influence the binding of 3H-QNB to the striatal muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of propofol for electroejaculation in domestic cats

The objective was to evaluate the use of propofol as an anesthetic drug for electroejaculation in the domestic cat. Cortisol concentrations, heart rates and respiratory rates of 20 male domestic cats were examined. The animals were randomly allocated into three groups. Group A (n = 8), were anesthetized with propofol (10 mg/kg) and underwent electroejaculation. Group B (n = 6), were pre-medicated with buprenorphine (0.01 mg/kg), anesthetized with propofol (5 mg/kg) and underwent electroejaculation. Group C (n = 6), the cats were anesthetized with propofol (10 mg/kg) without electroejaculation (control group). Blood samples were collected at four time points (30 min before propofol administration, immediately after the surgical plane of anesthesia was induced, immediately post-electroejaculation, and at the onset of anesthetic recovery). In the control group, the sampling time coincident with the end of electroejaculation was assigned as 21 min after the induction of anesthesia. The mean (+/- S.E.M.) duration time for electroejaculation was 18 +/- 3 min. The duration of anesthesia did not differ (P > 0.05) among the three groups of cats (26 +/- 2 min). Most of the cats (17/20) recovered smoothly. Pre-anesthetic medication with buprenorphine did not reduce the requirement of propofol for anesthesia. The cortisol concentrations, heart rates and respiratory rates of the three groups of cats did not differ (P > 0.05). A marked decline in cortisol levels was observed immediately post-electroejaculation. Propofol was a useful anesthetic for electroejaculation in felids with rapid onset, optimal duration of anesthesia for performing electroejaculation, and smooth recovery.     

Kinetic analyses demonstrate that the equilibrium assumption does not apply to [125I]endothelin-1 binding data.

The kinetics of [125I]Endothelin-1 ([125I]ET-1) binding were studied using membranes from rat heart, rat lung, rat brain, and porcine vascular smooth muscle at 37 degrees C in 0.05M Tris-HCl buffer (pH = 7.4). The dissociation half-life (t1/2, diss.) for bound [125I]ET-1 was in excess of 30 hours for each tissue studied. Equilibrium-time requirements for proper Scatchard analysis of [125I]ET-1 were also far in excess of 30 hours for each tissue. These data suggest that determination of dissociation constants, Kd, and receptor concentrations, Bmax, by conventional Scatchard analysis is not feasible with [125I]ET-1. Kinetic analyses may provide a more accurate means for determining [125I-ET-1] binding characteristics including Kd and Bmax.     

Inhibitory effects of propofol on neuron firing activities in the rostral ventrolateral medulla

The effect of propofol on neuronal activity in the rostral ventrolateral medulla (RVLM) is not well established. Therefore, we performed extracellular recording on neurons of the RVLM to investigate neuronal activity before and after administration of intravenous propofol. The mean systemic arterial pressure (MSAP), heart rate and integrated neuronal firing rate (INFR) in the RVLM were continuously recorded in anesthetized cats before and after intravenous injection of 2 mg/kg propofol or supplemental injections of 1, 2 and 4 mg/kg propofol that were given respectively. Additionally, we compared the MSAP, heart rate (HR), and INFR in the RVLM following intravenous injection of 2 mg/kg propofol or 12.5 microg/kg nitroprusside. Neuronal firing was dose-dependently and reversibly inhibited after the supplemental doses of 1, 2 and 4 mg/kg propofol. The control INFR was 14.2 +/- 9.9 Hz, and this decreased to 12.1 +/- 9.4 Hz after the first dose of propofol (P = 0.085 vs. control), and further decreased to 9.3 +/- 7.7 Hz (P = 0.001 vs. control) and 7.5 +/- 7.7 Hz (P < 0.001 vs. control) after the second and third doses of propofol, respectively. Besides, SAP and HR were dose-dependently decreased by propofol as well. However, the effects of propofol and nitroprusside on neuronal activity in the RVLM differed. Propofol inhibited neuronal firing, whereas nitroprusside activated neuronal firing. In conclusion, propofol may dose-dependently inhibit spontaneous neuronal activity and the baroreflex in the RVLM.     

小剂量利多卡因在无痛宫腔镜术中的应用

目的：观察静注利多卡因在无痛宫腔镜术的应用效果。方法：120例择期宫腔镜手术患者,随机均分为L、C两组。L组麻醉诱导前缓慢静脉推注利多卡因1mg／kg;C组以生理盐水替代。两组均静注丙泊酚1—1．5mg／kg进行麻醉诱导至睫毛反射消失,术中酌情追加丙泊酚。麻醉开始后,询问患者是否有静脉注射痛,观察记录术中及术后疼痛情况。结果：两组术中血压、心率平稳。L组较C组丙泊酚注射痛及术中术后疼痛程度减轻（P〈0．05）。结论：利多卡因复合丙泊酚用于无痛宫腔镜不良反应小,有利于病人术后恢复。     

Strain-dependent beta-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice

Recently, we showed that compared with the A/J inbred mouse strain, C57BL/6J (B6) mice have an athlete's cardiac phenotype. We postulated that strain differences would result in greater left ventricular (LV) hypertrophy in response to isoproterenol in B6 than A/J mice and tested the hypothesis that a differential response could be explained partly by differences in beta-adrenergic receptor (beta-AR) density and/or coupling. A/J and B6 mice were randomized to receive daily isoproterenol (100 mg/kg sc) or isovolumic vehicle for 5 days. Animals were studied using echocardiography, tail-cuff blood pressure, histopathology, beta-AR density and percent high-affinity binding, and basal and stimulated adenylyl cyclase activities. One hundred twenty-eight mice (66 A/J and 62 B6) were studied. Isoproterenol-treated A/J mice demonstrated greater percent increases in echocardiographic LV mass/body weight (97 +/- 11 vs. 20 +/- 10%, P = 0.001) and in gravimetric heart mass/body weight versus same-strain controls than B6 mice. Histopathology scores (a composite of myocyte hypertrophy, nuclear changes, fibrosis, and calcification) were greater in isoproterenol-treated A/J vs. B6 mice (2.8 +/- 0.2 vs.1.9 +/- 0.3, P < 0.05), as was quantitation of myocyte damage (22.3 +/- 11.5 vs. 4.3 +/- 3.5%). Interstrain differences in basal beta-AR density, high-affinity binding, and adenylyl cyclase activity were not significant. However, whereas isoproterenol-treated A/J mice showed nonsignificant increases in all beta-AR activity measures, isoproterenol-treated B6 mice had lower beta-AR density (57 +/- 6 vs. 83 +/- 8 fmol/mg, P < 0.05), percent high-affinity binding (15 +/- 2 vs. 26 +/- 3%, P < 0.005), and GTP + isoproterenol-stimulated adenylyl cyclase activity (10 +/- 1.1 vs. 5.8 +/- 1.5 pmol cAMP.mg(-1).min(-1)) compared with controls. High-dose, short-term isoproterenol produces greater macro- and microscopic cardiac hypertrophy and injury in A/J than B6 mice. A/J mice, unlike B6 mice, do not experience beta-AR downregulation or uncoupling in response to isoproterenol. Abnormalities in beta-adrenergic regulation may contribute to strain-related differences in the vulnerability to isoproterenol-induced cardiac changes.     

125I-labelled hCG binding characteristics in theca interna and other tissues from Romney ewes and from Booroola x Romney ewes with and without a major gene influencing their ovulation rate

Specific receptors for 125I-labelled hCG in ovarian follicle wall were located in the theca interna. No specific binding of 125I-labelled hCG was found in theca externa and/or stromal tissue. The kinetics of 125I-labelled hCG binding to theca interna followed second order kinetics with calculated association rate constants (ka +/- s.d.) of 1.57 +/- 0.16 X 10(6) and 0.57 +/- 0.02 X 10(6) litres mol-1 sec-1 at 37 degrees C and 22 degrees C respectively. Dissociation of specifically bound 125I-labelled hCG from theca interna was minimal at 37 degrees C and 22 degrees C. The binding of 125I-labelled hCG to theca interna could be displaced with PMSG, FSH-P and sheep LH but other sheep pituitary hormones and LH-releasing hormone showed little or no cross-reaction. The calculated binding capacities (Bmax) and equilibrium dissociation constants (Kd) for 125I-labelled hCG binding to theca interna did not differ between Romney ewes and Booroola x Romney ewes with and without the fecundity (F) gene on Day 10 of the oestrous cycle, during anoestrus or at 36 h after an injection of cloprostenol on Day 10 of the oestrous cycle. When the data for Day 10 and anoestrus were pooled, the median (range) Bmax and Kd values in non-atretic follicles (greater than or equal to 3 mm diameter) were 12.0 (5.1-23.5) fmol/mg protein and 0.10 (0.05-0.16) nM respectively. At 36 h after cloprostenol injection the respective median (range) Bmax and Kd values in non-atretic follicles (greater than or equal to 3 mm diam.) increased to 46.9 (28.4-70.3) fmol/mg protein and 0.23 (0.13-0.65) nM respectively. In corpora lutea the hCG binding characteristics were similar in all the above breeds/genotypes. On Day 10 of the cycle, the mean Bmax but not the mean Kd value was significantly higher (P less than 0.01) than the corresponding value at 36 h after cloprostenol injection. In granulosa cells, from follicles of greater than or equal to 5 mm diameter of Romney and Booroola x Romney (++) ewes and from follicles of greater than or equal to 3 mm diameter of Booroola x Romney (F+) ewes, the hCG binding characteristics were similar. In granulosa cells from smaller sized follicles from the above breeds/genotypes, no specific hCG binding was noted.     

Modulation of 3H-prostaglandin E2 binding sites in the rabbit gastric mucosa

The binding of 3H-prostaglandin E2 (PGE2) to rabbit gastric mucosa was investigated. Binding depended on incubation time, temperature and pH, and was saturable and reversible. Scatchard plot analysis revealed a single class of binding sites with a dissociation constant (Kd) of 5.33 +/- 0.21 nM and a maximum number of binding sites (Bmax) of 138.1 +/- 3.4 fmol/mg protein. PGE1 and 16,16-dimethyl PGE2 potently competed with 3H-PGE2 for the binding sites of gastric mucosa, whereas PGA2, PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2 were less potent. The gastric mucosa prepared from the rabbits given indomethacin (5 mg/kg s.c. three times) showed a lower Kd (2.47 +/- 0.19 nM) for 3H-PGE2 than that from untreated one. Treatment with a PGE1 analog, misoprostol (320 micrograms/kg s.c. three times) lowered the Bmax to 74.1 +/- 2.4 fmol/mg protein without any significant effect on the Kd value. It is concluded that rabbit gastric mucosa has specific binding sites for 3H-PGE2 which may be modulated by the levels of PGs in vivo.