垂体后叶素和加压素对离体心肌的直接作用

本实验采用大鼠离体右心房和右心室肌条模型,观察了垂体后叶素和加压素对右心房和右心室肌的直接作用。结果表明:垂体后叶素对右心房的自主性收缩频率和幅度及右心室肌的收缩幅度均有剂量依赖性抑制作用;加压素对右心房和右心室肌收缩幅度也有剂量依赖性抑制作用,但对右心房自主节律无影响;催产素对右心房的收缩频率和幅度则均无影响。加压素V_1、V_2受体拮抗剂d(CH_2)_5Tyr(Me)AVP和d(CH_2)_5(D-Ile~2,Ile~4,Ala(NH_2)~9)AVP对垂体后叶素的负性变力作用具有不同程度的阻断作用,但对垂体后叶素的负性变时作用无阻断作用。以上结果提示,垂体后叶素的负性变力作用主要是由加压素产生的,加压素对心肌有直接的负性变力作用;垂体后叶素的负性变时作用可能是非加压素和催产素成分的作用结果。     

Vanadate as an activator of ATP — sensitive potassium channels in mouse skeletal muscle

The inside-out mode of the patch-clamp technique was used to study adenosine-5-triphosphate (ATP)-sensitive K⁺ channels in mammalian skeletal muscle. Vanadate, applied to the cytoplasmic face of excised patches, was a potent activator of ATP-sensitive K⁺ channels. Divalent cations (Mg²⁺, Ca²⁺) were a prerequisite for the activating process. The maximal effect was achieved using 1 mM vanadate dissolved in Ringer, increasing the open-state probability about ninefold. The active 5 + redox form of vanadate which stimulates ATP-sensitive K⁺ channels is likely to be decavanadate V₁₀O _inf28 ^sup6– . ATP concentration-response curves have Hill coefficients near three in internal Na⁺-rich Ringer and between one and two in internal KCl solutions. Half maximal channel blockage was observed at ATP concentrations of 4 and 8 M in Ringer and KCl solutions, respectively. Internal vanadate shifted the curves towards higher ATP concentrations without affecting their slopes. Thus 50% channel blockage occurred at 65 M ATP in internal Ringer containing 0.5 mM vanadate. The results indicate that the affinity and stoichiometry of ATP binding to ATP-sensitive K⁺ channels are strongly modulated by internal cations and that the ATP sensitivity is weakened by vanadate. Offprint requests to: B. Neumcke     

Interactions between intrinsic regulation and neural modulation of acetylcholinesterase in fast and slow skeletal muscles

1. Initiation of subsynaptic sarcolemmal specialization and expression of different molecular forms of AChE were studied in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle of the rat under different experimental conditions in order to understand better the interplay of neural influences with intrinsic regulatory mechanisms of muscle cells. 2. Former junctional sarcolemma still accumulated AChE and continued to differentiate morphologically for at least 3 weeks after early postnatal denervation of EDL and SOL muscles. In noninnervated regenerating muscles, postsynaptic-like sarcolemmal specializations with AChE appeared (a) in the former junctional region, possibly induced by a substance in the former junctional basal lamina, and (b) in circumscribed areas along the whole length of myotubes. Therefore, the muscle cells seem to be able to produce a postsynaptic organization guiding substance, located in the basal lamina. The nerve may enhance the production or accumulation of this substance at the site of the future motor end plate. 3. Significant differences in the patterns of AChE molecular forms in EDL and SOL muscles arise between day 4 and day 10 after birth. The developmental process of downregulation of the asymmetric AChE forms, eliminating them extrajunctionally in the EDL, is less efficient in the SOL. The presence of these AChE forms in the extrajunctional regions of the SOL correlates with the ability to accumulate AChE in myotendinous junctions. The typical distribution of the asymmetric AChE forms in the EDL and SOL is maintained for at least 3 weeks after muscle denervation. 4. Different patterns of AChE molecular forms were observed in noninnervated EDL and SOL muscles regenerating in situ. In innervated regenerates, patterns of AChE molecular forms typical for mature muscles were instituted during the first week after reinnervation. 5. These results are consistent with the hypothesis that intrinsic differences between slow and fast muscle fibers, concerning the response of their AChE regulating mechanism to neural influences, may contribute to different AChE expression in fast and slow muscles, in addition to the influence of different stimulation patterns.     

Evidence for the involvement of a SchistoFLRF-amide-like peptide in the neural control of locust oviduct

Summary The presence of a SchistoFLRFamide-like peptide associated with the oviducts of Locusta migratoria has been shown using sequential reversed-phase high performance liquid chromatography separation coupled with radioimmunoassay and bioassay. The peptide is present in areas of the oviduct which receive extensive innervation, with sixfold less peptide in areas that receive little innervation. Material with FMRFamide-like immunoreactivity (determined by radioimmunoassay) is also present in the oviducal nerve and VIIth abdominal ganglion.SchistoFLRFamide is a potent modulator of contraction of this visceral muscle, inhibiting or reducing the amplitude and frequency of spontaneous contractions, relaxing basal tonus, and reducing the amplitude of neurally-evoked, proctolin-induced, glutamate-induced and high potassium-induced contractions. The FMRFamide-like immunoreactivity within the oviducts which co-elutes with SchistoFLRFamide on two separations is also capable of reducing the amplitude of neurally-evoked and proctolin-induced contractions, and of inhibiting spontaneous contractions and relaxing basal tonus.The effects of SchistoFLRFamide upon this visceral muscle are not abolished by the -adrenergic receptor antagonist phentolamine and do not appear to be mediated by cyclic AMP. Thus the receptors for Schisto-FLRFamide are distinct from those of octopamine which mediate similar physiological effects but which are blocked by phentolamine and which are coupled to adenylate cyclase.The results indicate that SchistoFLRFamide, or a very similar peptide, which has previously been identified as a modulator of locust heart beat, is also associated with visceral muscle of the reproductive system, and may play a neural role in concert with octopamine, at modulating muscular activity.Abbreviations BPP Bovine pancreatic polypeptide - BSA Bovine serum albumin - EJP Excitatory junctional potential - FaRPs FMRFamide-related peptides - FLI FMRFamide-like immuno-reactivity - LMS Leucomyosuppressin - RIA Radioimmunoassay - RP-HPLC Reversed-phase high performance liquid chromatography - TFA Trifluoroacetic acid     

Ionic transporting systems of skeletal muscle in relation with innervation and their involvement in myotonic diseases

Excitation-contraction coupling describes the series of events that begins with propagated action potential on the muscle fiber surface membrane and leads to the twitch contraction of the fiber. The generation of an action potential during excitation requires rapid sequential changes in membrane conductances of Na⁺, Ca²⁺, and K⁺ ions that depend upon the opening and closing of the respective channels. Myotonic disorders are inherited diseases whose clinical manifestations include electrophysiological signs such as increased excitability and delayed relaxation of the muscles after voluntary contraction. All these disorders appears to be due to an abnormality of the muscle itself since they persist after section or blocking of the motor nerve after curarization. Most experimental and clinical data suggest that human myotonia arises from genetically-induced structural and functional alterations of the muscle membrane. The purpose of this article is to focus on the more recent developments in the molecular and pharmacological analysis of cation transporting systems such as ionic channels and (Na⁺, K⁺) ATPase in myotonic disorders.Special issue dedicated to Dr. Lawrence Austin.     

氯化钠对培养的大鼠主动脉平滑肌细胞的心房钠尿肽受体的调节

培养的卒中型自发性高血压大鼠(SHR_(sp))及其对照 WKY 大鼠主动脉平滑肌细胞(VSMC)上存在心房钠尿肽(ANP)的特异性受体,它们与~(125)I-ANP 的最大结合量(B_(max))是:SHR_(sp)3.65±0.13和 WKY 1.89±0.09 pmol/mg pr(P<0.01);解离平衡常数(Kd)值分别是72.6±10.2和42.0±4.8×10~(-12)mol/L(P<0.01)。 两种细胞内介导舒血管作用的第二信使、环磷酸乌苷(cGMP)的基础浓度无显著差异,对相同剂量 ANP 刺激引起 cGMP 分别增加139(SHRsp)和271(WKY)倍。可见 SHRsp 的 VSMC ANP 受体数量虽比 WKY大鼠增多,但对相同剂量 ANP 引起的 cGMP 增加反应及 ANP 受体的亲和力均显著降低。高盐培养液孵育24h 后,细胞表面 ANP 受体的亲和力改变不明显,但受体数量下调,SHRsp 和 WKY 大鼠分别降至对照的34.8±8.2%和38.6±9.4%,细胞对 ANP 引起的 cGMP增加反应明显降低,且均以 SHR_(sp)较显著。提示后两种变化可能在高盐促进血压升高的机制中起作用。     

大鼠离体乳头肌收缩末期张力—长度关系的曲线性

大鼠离体左室乳头肌固定于最适初长位,逐步递减“后荷”获得一系列等张收缩的张力、长度缩短程度和速度。结果发现:(1)收缩末期张力-长度关系(ESTLR)为指数曲线,回归方程 T=ar~(-bL)-K 拟合的优度明显高于线性方程拟合的优度(P<0.001),其中 a,k 分别代表总张力和静息张力,b 为曲线的弯曲度;(2)在高钙(4mmol/L)或去甲肾上腺素(NE10~(-6)mol/L)作用下,ESTLR 右上移位,a,b 和无张力缩短速度 L_O 均增大(P均<0.01),尤以高钙时的变化更明显,(3)NE 使张力-速度曲线的右上移位比高钙显著。这提示大鼠离体心肌的 ESTLR 呈非线性特征,参数 a,b 及长度轴截距 L_O 对收缩强度的变化敏感,但对收缩速度改变的敏感性可能比经典的力学指标低。     

Issues related to mineralized tissue biology in human evolutionary research

This comunication has two primary aims concerned with mineralized tissue biology (e.g. hard tissue biology of bone and tooth) research in human evolutionary studies: First, to introduce the literature and the methods (at the time of this symposium) so that one has an idea of the nature of this research and where one can go for details of the methodologies, etc; Second — and of primary concern here — to discuss issues that have come to light as a result of these studies mainly because of its recent beginnings as a subfield within paleoanthropology. Issues related to skeletal studies include; 1) whether different cortical surface pattens and bone tissue types influence the appearance and interpretation of bone growth activity states; 2) if SEM analyses of cortical surfaces in fossil hominids allow one to construct meaningful representations of remodeling patterns; 3) whether these representations can be used in phylogenetic arguments; and 4) how intraspecific variability would affect these issues. Issues related to dental studies include: 1) the relationship between the rate and pattern of eraly hominid dental development; 2) experimental support for the calibration of eraly hominid dental developmental rates; and 3) whether replica techniques are suitable for microanatomical studies of these sorts.     

On estimating mortalities from osteological age data

A statistical method (based on the maximum likelihood principle) for estimating mortalities of skeletal populations is presented. The method can be applied both when osteological age groups are not overlapping as well as when they are. The results are presented as point estimates and as confidence intervals around these. The method is applied to two series from the Middle Ages: Westerhus and Helgeandsholmen.     

Secretion of a new growth factor, smooth muscle cell derived growth factor, distinct from platelet derived growth factor by cultured rabbit aortic smooth muscle cells

In attempts to determine the mechanism of proliferation of arterial smooth muscle cells (SMC) in intimal atheromatous lesions, autocrine secretion of growth factors by SMC has recently received much attention. Here we report a new growth factor named smooth muscle cell derived growth factor (SDGF). Cultured rabbit medial SMC secreted SDGF for 1 week during their incubation in serum-free media only after at least 4 passages. SDGF differed from platelet derived growth factor (PDGF) physicochemically, immunologically, and biologically. The properties of SDGF also seemed different from those of other known growth factors that stimulate the proliferation of mesenchymal cells.