Vasoactive intestinal polypeptide and muscarinic receptors: supersensitivity induced by long-term atropine treatment

Long-term treatment of rats with atropine induced large increases in the numbers of muscarinic receptors and receptors for vasoactive intestinal polypeptide in the salivary glands. Since receptors for vasoactive intestinal polypeptide coexist with muscarinic receptors on the same neurons in this preparation, the results suggest that a drug that alters the sensitivity of one receptor may also affect the sensitivity of the receptor for a costored transmitter and in this way contribute to the therapeutic or side effects of the drugs.     

Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers

Neural control of bone metabolism and growth has been suggested, although the identity of participating neurons and neurotransmitters effecting this control has not been established. Immunohistochemical studies demonstrated a system of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers that innervate periosteum and bone in several mammalian species. Thoracic sympathetic chain ganglionectomy resulted in an ipsilateral loss of VIP-immunoreactive fibers in the periosteum of ribs, whereas dorsal root ganglionectomy had no effect. Injection of fast blue into rib periosteum labeled a population of VIP-immunoreactive sympathetic postganglionic neurons. Thus, postganglionic sympathetic neurons may provide an important means by which VIP regulates bone mineralization.     

新生儿颅内出血患者血浆、脑脊液中生长抑素和血管活性肠肽的测定及意义

目的观察新生儿颅内出血患者血浆、脑脊液(CSF)中生长抑素(SS)和血管活性肠肽(VIP)的水平变化与临床意义。方法应用放射免疫法对19例新生儿颅内出血患儿的血浆、脑脊液SS和VIP的含量作了测定,并与以无神经系统疾病的入院新生儿12例作为对照。结果颅内出血新生儿CSF的SS和VIP含量高于其在血浆中的含量(P<0.01);颅内出血急性期患儿血浆和CSF的SS和VIP含量均显著高于恢复期和对照组,恢复期又显著高于对照组,差异均有统计学意义(P<0.01)。结论血浆、CSF中SS和VIP含量的变化可反映脑组织损伤的分期,推测病情和预后。     

Slow synaptic excitation in sympathetic ganglion cells: evidence for synaptic inactivation of potassium conductance

The slow excitatory postsynaptic potential (EPSP) was investigated in frog sympathetic ganglion cells. In contrast to the increased conductance associated with other known EPSP's, during the slow EPSP resting membrane conductance was decreased. Electrical depolarization of the membrane potentiated the slow EPSP, whereas progressive hyperpolarization decreased its size and then reversed it to a hyperpolarizing potential (the opposite of the effect of membrane polarization on other EPSP's). The reversal potential of the slow EPSP was close to the potassium equilibrium potential. We propose that the slow EPSP, in contrast to classical EPSP's, is generated by an inactivation of resting potassium conductance.     

Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody

Vasoactive intestinal peptide (VIP) labeled with 125I, [Tyr10-125I]VIP, can be hydrolyzed by immunoglobulin G (IgG) purified from a human subject, as judged by trichloroacetic acid precipitation and reversed-phase high-performance liquid chromatography (HPLC). The hydrolytic activity was precipitated by antibody to human IgG, it was bound by immobilized protein G and showed a molecular mass close to 150 kilodaltons by gel filtration chromatography, properties similar to those of authentic IgG. The Fab fragment, prepared from IgG by papain treatment, retained the VIP hydrolytic activity of the IgG. Peptide fragments produced by treatment of VIP with the antibody fraction were purified by reversed-phase HPLC and identified by fast atom bombardment-mass spectrometry and peptide sequencing. The scissile bond in VIP deduced from these experiments was Gln16-Met17. The antibody concentration (73.4 fmol per milligram of IgG) and the Kd (0.4 nM) were computed from analysis of VIP binding under conditions that did not result in peptide hydrolysis. Analysis of the antibody-mediated VIP hydrolysis at varying concentrations of substrate suggested conformity with Michaelis-Menton kinetics (Km). The values for Km (37.9 X 10(-9) M) and the turnover number kcat (15.6 min-1) suggested relatively tight VIP binding and a moderate catalytic efficiency of the antibody.     

Generation of adrenergic and cholinergic potentials in sympathetic ganglion cells

Norepinephrine elicited a hyperpolarizing response, and acetylcholine (during nicotinic blockade) elicited a depolarizing one. Both responses showed no increase in membrane conductance. The norepinephrine response was suppressed by initial depolarization; the acetylcholine response (frog cells); by hyperpolarization. These neurotransmitters apparently can activate electrogenic mechanisms which do not involve movement of ions down their electrochemical gradients.     

Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide

Vasoactive intestinal peptide caused a prompt, dose-dependent relaxation of isolated gastric smooth muscle cells of the guinea pig and a significant increase in intracellular adenosine 3',5'-monophosphate coincidentally with optimum relaxation. Relaxation was augmented by a threshold concentration of isobutyl methylxanthine. The direct relaxant effect of vasoactive intestinal peptide and the distribution of nerves containing this peptide to circular smooth muscle support the view that vasoactive intestinal peptide is the neuromuscular transmitter of enteric inhibitory nerves.     

鸡血管活性肠肽RNA探针制备及其在鸡肠Remak神经的原位杂交反应

应用RT-PCR方法从鸡脑中扩增血管活性肠肽(VIP)基因片段,将其连接于pGM-T easy.分别利用pGM-T easy中T7和SP6启动子及其RNA聚合酶,以线性化的VIP/pGM-T easy为模板转录合成正、反义DIG标记RNA探针.通过原位杂交方法将合成的探针用于探查VIP-mRNA在鸡肠Remak神经(INR)中的分布情况.结果表明,INR的神经元胞体中有VIP-mRNA的转录,且这种神经元数量众多;原位杂交阳性神经元胞体大部分是大型神经元细胞,呈圆形或椭圆形;阳性神经元胞体在INR神经节中呈层状或成群分布.INR的神经纤维呈弱阳性.在节间束也有少量的阳性细胞分布.本研究从基因水平证明INR中有VIP神经元存在.     

Cardiac sympathetic nerve activity: changes induced by ouabain and propranolol

A study of the effects of ouabain and propranolol on the spontaneous activity in the preganglionic sympathetic nerves to the cat heart showed that ouabain can produce both an inhibition and a stimulation of the spontaneous activity in sympathetic nerves. The inhibition appears to be reflex in nature and is not present when the buffer nerves are sectioned. The stimulation is correlated with the development of cardiac arrhythmias and is antagonized by propranolol.     

鸡肠道组织中血管活性肠肽的分布特点

为探讨鸡肠道组织中肽能神经支配的途径及其功能,运用免疫组织化学超敏SP法,对不同生长阶段鸡肠道中血管活性肠肽(Vasoactive intestinal peptide,VIP)的分布特点进行了研究。结果显示,肠壁中VIP的表达范围较为广泛,涉及黏膜上皮和固有层、肌层和外膜,尤以固有层和肌层最为典型;随着日龄增加,黏膜上皮间VIP阳性细胞数量逐渐增多;从肠道不同部位的分布来看,十二指肠中VIP的表达强于同时期其他部位,空肠中的表达次之,回肠和盲肠的表达相对较弱。黏膜固有层和肌层一直分布有染色较深的VIP阳性神经纤维,呈串珠状、细线状或膨体状。提示鸡肠道是产生VIP的又一个重要部位,肠道中的VIP可参与鸡免疫器官的功能调节,并作为一种信息分子介导神经内分泌系统和黏膜免疫系统之间的相互作用。     

Lateral hopping of molecules induced by excitation of internal vibration mode

We demonstrate electron-stimulated migration for carbon monoxide (CO) molecules adsorbed on the Pd(110) surface, which is initiated by the excitation of a high-frequency (HF) vibrational mode (C-O stretching mode) with inelastic tunneling electrons from the tip of scanning tunneling microscopy. The hopping phenomenon, however, cannot be detected for CO/Cu(110), even though the hopping barrier is lower than in the CO/Pd(110) case. A theoretical model, which is based on the anharmonic coupling between low-frequency modes (the hindered-translational mode related to the lateral hopping) and the HF mode combined with electron-hole pair excitation, can explain why the hopping of CO is observed on Pd(110) but not on Cu(110).     

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.     

鸡法氏囊中血管活性肠肽的表达特点

运用免疫组织化学超敏SP法对鸡不同生长阶段法氏囊中血管活性肠肽(VasoactiveIntestinal Peptide,VIP)的表达特点进行了研究。结果显示,法氏囊中VIP的表达范围广泛,涉及黏膜、黏膜下层和肌层,尤以黏膜上皮细胞和法氏囊小结髓质的表达为典型;随着日龄增加,黏膜上皮细胞VIP表达逐渐减弱,囊小结髓质一直保持较强的VIP阳性着色,囊小结皮髓质交界处上皮细胞层内VIP强阳性细胞有逐渐增多的趋势。鸡法氏囊中VIP阳性反应物质的广泛分布,提示法氏囊是神经系统以外产生VIP的又一个重要部位,法氏囊中的VIP可参与鸡免疫器官的功能调节,可作为一种信号分子介导神经内分泌系统和免疫系统间的相互作用。     

Deficient vasoactive intestinal peptide innervation in the sweat glands of cystic fibrosis patients

The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide-containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.     

Failure of beta-adrenergic receptor blockade to prevent arrhythmias induced by sympathetic nerve stimulation

Cardiac arrhythmias produced by electrical stimulation of the ventrolateral cardiac sympathetic nerve in dogs were not blocked by the combined administration of propranolol and practolol in amounts that completely blocked cardiac beta-adrenergic receptors. Blockade of cardiac alpha-adrenergic receptors, as well as cardiac cholinergic receptors, also had no influence on the arrhythmias. These results suggest that the adrenergic neuroeffector junction is fundamentally different from any hitherto described, differing perhaps in the neurotransmitter involved or in the nature of the receptor.     

Amino acid changes provoked by streptomycin in a polypeptide synthesized in vitro

The misincorporation of isoleucine provoked by streptomycin in a polyuridylate-directed incorporating system from Escherichia coli has been examined by a double-labeling technique with phenylalanine-(3)H and isoleucine-(14)C. The polypeptides synthesized are associated with 70S ribosomes and contain only phenylalanine in the absence of streptomycin, and both phenylalanine and isoleucine in the presence of the antibiotic. Results of acid hydrolysis and subsequent chymotryptic digestion of the polypeptides indicate that the misincorporated amino acid is inserted by peptide bonding with phenylalanine and is randomly distributed along the chain.     

Hyperphagia in ruminants induced by a depressant

Attempts at causing ventromedial hyperphagia in ruminants have been hitherto unsuccessful. In our experiments perfusion of the ventriculocisternal system with pentobarbital caused marked hyperphagia. This suggests that the ventromedial hypothalamic area is functioning in ruminants, probably as in monogastric animals, by inhibiting the lateral area.     

Blockade of visual excitation and adaptation in Limulus photoreceptor by GDP-beta-S

Light causes both depolarization and adaptation to light in Limulus ventral photoreceptors. Both visual excitation and adaptation were blocked by guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), a metabolically stable analog of guanosine 5'-diphosphate (GDP). However, GDP-beta-S did not block the excitation caused by injection of inositol 1,4,5-trisphosphate into the cell. These results suggest a molecular cascade of visual excitation and adaptation: Light isomerizes the visual pigment rhodopsin, which in turn activates a guanyl nucleotide-binding protein. The binding protein then stimulates production of inositol 1,4,5-trisphosphate, which causes release of calcium from the endoplasmic reticulum.     

Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide

The presurface (preS) proteins of hepatitis B virus are structural components of the viral envelope that may play important roles in virion assembly and infectivity. They are specified by a large open reading frame that includes the coding region for the major surface (S) protein in its 3' half. Translation of the preS proteins initiates upstream from the S region, giving rise to proteins that are composed of the S domain and an additional 163 (preS1) or 55 (preS2) amino acids. Little is known about the biosynthesis and assembly of these proteins. The expression of the S and preS1 proteins was examined by transfecting cultured mammalian cells with viral DNA and injecting synthetic messenger RNA's into Xenopus oocytes. In contrast to the proteins encoded by the S region, the preS1 proteins are not detectably secreted into the culture medium. Furthermore, when the S and preS1 proteins are synthesized together, secretion of the S proteins is specifically and strongly inhibited. The results suggest a unique molecular interaction during secretion of the S and preS proteins that may be important for virus assembly.