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1.
Octapeptide analogs of somatostatin exhibiting greatly enhanced in vivo and in vitro inhibition of growth hormone secretion in the rat 总被引:1,自引:0,他引:1
W A Murphy M L Heiman V A Lance I Mezo D H Coy 《Biochemical and biophysical research communications》1985,132(3):922-928
Analogs of a superactive somatostatin (SRIF) octapeptide (code named SMS 201-995 (1)) were synthesized using solid-phase synthetic methodology and assayed for their ability to inhibit growth hormone release from cultured rat anterior pituitary cells and in sodium pentobarbital-anesthetized rats. One analog: (Formula: see text) exhibited greatly enhanced in vitro inhibitory activity (greater than 1,000x) relative to both the parent octapeptide molecule and to the 14 amino acid SRIF molecule. This analog which was also very potent in vivo contains a tyrosine residue and, given its high in vitro activity, may be of investigative importance as a radioiodinated ligand in receptor assays. An octapeptide retro-inverso analog also exhibited significant SRIF-like activity. Several very low activity octapeptide analogs were synthesized and were found to be devoid of SRIF-antagonist activity. A dodecapeptide analog previously shown to be superactive in vivo also demonstrated high in vitro activity. 相似文献
2.
M L Heiman W A Murphy M V Nekola V A Lance D H Coy 《Biochemical and biophysical research communications》1984,124(1):217-222
The aim of this study was to investigate whether anterior pituitary responsiveness to human pancreatic growth hormone-releasing factor containing 29 amino acids (GRF-29) can be modulated by GRF-29 itself. Male rats were injected (sc) daily for 3 days with 50 ug of GRF-29, or were treated twice daily for 14 days with 5 ug of [D-Ala-2]-GRF-29 (a potent GRF agonist). Control animals were injected with saline. After the last injection, pituitaries were removed, dispersed, cultured for 96 h and then challenged with either GRF-29 or [D-Trp-6]-LHRH (a LHRH agonist). Cultured cells from analog-treated rats were more responsive to GRF-29 stimulation than were cells obtained from controls. In contrast, neither treatment altered the response to [D-Trp-6]-LHRH. These studies indicate that periodic administration of GRF analogs can increase hypophyseal GRF responsiveness. Such control may be an important component in the physiological regulation of GH secretion and has important implications for potential therapeutic uses of GRF analogs. 相似文献
3.
Isolation and characterization of a large,neurite-associated glycoconjugate from neuroblastoma cells 下载免费PDF全文
A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species. 相似文献
4.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
5.
Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability 总被引:14,自引:0,他引:14
We have analyzed nucleic acid and amino acid sequence alignments of a
variety of voltage-sensitive ion channels, using several methods for
phylogenetic tree reconstruction. Ancient duplications within this family
gave rise to three distantly related groups, one consisting of the Na+ and
Ca++ channels, another the K+ channels, and a third including the cyclic
nucleotide-binding channels. A series of gene duplications produced at
least seven mammalian homologues of the Drosophila Shaker K+ channel;
clones of only three of these genes are available from all three mammalian
species examined (mouse, rat, and human), pointing to specific genes that
have yet to be recovered in one or another of these species. The
Shaw-related K+ channels and the Na+ channel family have also undergone
considerable expansion in mammals, relative to flies. These expansions
presumably reflect the needs of the high degree of physiological and
neuronal complexity of mammals. Analysis of the separate domains of the
four-domain channels (Ca++ and Na+) supports their having evolved by two
sequential gene duplications and implies the historical existence of a
functional two-domain channel.
相似文献
6.
mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species 总被引:4,自引:0,他引:4
Reconstructions of the human-African great ape phylogeny by using
mitochondrial DNA (mtDNA) have been subject to considerable debate. One
confounding factor may be the lack of data on intraspecific variation. To
test this hypothesis, we examined the effect of intraspecific mtDNA
diversity on the phylogenetic reconstruction of another Plio- Pleistocene
radiation of higher primates, the fascicularis group of macaque (Macaca)
monkey species. Fifteen endonucleases were used to identify 10 haplotypes
of 40-47 restriction sites in M. mulatta, which were compared with similar
data for the other members of this species group. Interpopulational,
intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of
divergence time and branching order incorporating this variation were
substantially different from those based on single representatives of each
species. We conclude that intraspecific mtDNA diversity is substantial in
at least some primate species. Consequently, without prior information on
the extent of genetic diversity within a particular species, intraspecific
variation must be assessed and accounted for when reconstructing primate
phylogenies. Further, we question the reliability of hominoid mtDNA
phylogenies, based as they are on one or a few representatives of each
species, in an already depauperate superfamily of primates.
相似文献
7.
An aqueous extract of bovine pineal tissue contained a principle which caused a potent inhibition of ACTH mediated corticosterone release by isolated adrenal cells, whereas a similar extract of cortical tissue did not have any effect on this process. Two pineal indoles were tested. Melatonin (10?8 M) did not have any significant effect, whereas 5-methoxytryptophol (10?8 M) caused a variable but significant additive effect on ACTH mediated corticosterone release. We are uncertain at the present time if this principle is similar to the reported pinealantigonadotropin. 相似文献
8.
Cytosols from 7, 12-dimethylbenz (alpha) anthracene-induced rat mammary tumors which exhibit different hormone-responsiveness were compared with respect to their cAMP-dissociation kinetics. At 22 degree C, pH 4.5, 1 micrometer cAMP, hormone-dependent mammary tumors exhibited monophasic dissociation rates with a rate constant of k-1 = 0.06 min-1. In contrast, hormone-independent mammary tumors exhibited biphasic dissociation curves with rate constants of k-1 = 0.47 and k-2 = 0.06 min-1. The binding of cAMP was completely reversible; radio-labeled ligand was completely dissociated by 1mM nonradioactive cAMP; the binding protein could be reassociated to its original binding level after dextran-coated charcoal adsorption. The mammary cytosols exhibited specific binding for cAMP which could be displaced partially by cGMP but not by ATP, ADP, AMP, or adenosine. Receptor inactivation during the course of incubation was negligible. Both mammary tissue cytosols exhibited similar association rates at 22 degree C, pH 4.5, 1 micrometer cAMP (k+1 = 5-7 x 10(5)M-1 min-1). These data indicate that mammary tissues exhibit 2 cAMP dissociation rates. Hormone-dependent mammary tumors exhibit a dissociation constant of a high affinity binding site (k-1/k+1 = 0.07 micrometer) whereas hormone-independent mammary tumors exhibit dissociation constants of one high affinity (k-1/k+1 = 0.07 micrometer) and a second low affinity site (k-1/k+1 = 0.05 micrometer). 相似文献
9.
10.
Steroid acid esters, synthesized by modifying the 17-ketol side chain of prednisolone, were tested for their in vitro ability to stabilize heavy mitochondrial lysosomes prepared from rat liver. Membrane stabilization was determined by assessing capability of steroids to decrease extrusion of the marker enzymes (acid phosphatase, beta-glucuronidase and aryl sulfatase) from lysosomes incubated in hypo-osmotic sucrose-Tris acetate buffer. Results indicated that prednisolone (1) significantly inhibited the lysosomal release of acid phosphatase as did the new anti-inflammatory steroid, methyl 20-dihydroprednisolonate. Methyl prednisolonate exhibited weak membrane stabilization capacities and 20-dihydroprednisolonic acid, a metabolic product of methyl 20-dihydroprednisolonate, showed virtually no membrane stabilization. 相似文献