Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The somatostatin analogs D-Phe-Cys-D-Trp-Lys-Thr-Cys-Thr and the corresponding penicillamine compounds have been prepared and tested for their ability to displace [3H]naloxone and [3H] [D-Ala2, D-Leu5]enkephalin from rat brain receptors. While somatostatin and the cystine containing peptide displayed little or no preference for either receptor system, the substitution of penicillamine at position two or seven resulted in analogs that displayed opposite receptor selectivity. The substitution of tyrosine for phenylalanine at position three resulted in a large increase in opiate receptor affinity which may be related to the known requirement for a phenolic hydroxyl moiety in the rigid opiate and enkephalin systems. Conformational properties of these analogs were also examined and related to their affinity for opiate and somatostatin receptors in the rat brain.
 ...
PMID:Somatostatin analogs with affinity for opiate receptors in rat brain binding assay. 286 80

The antisecretory properties of opiates in the guinea-pig ileum have been shown previously to be mediated through interactions with delta-like opiate receptors present in the intestinal mucosa. The present investigation examined the development of tolerance to opioid-induced alterations in intestinal ion transport processes. Osmotic minipumps continuously delivering the prototypic delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) (5 micrograms/hr) or the potent mu-opiate agonist fentanyl (10 micrograms/hr) over a 5-day period were implanted s.c. into guinea pigs; control animals did not receive chronic drug infusions. DADLE, DADLE ethylamide and [D-Ala2,D-Met5]enkephalin dose-dependently decreased base-line transepithelial potential difference and short-circuit current in isolated segments of ileal mucosa from untreated control animals, with an order of potency of DADLE greater than [D-Ala2, D-Met5 enkephalin greater than DADLE ethylamide. In tissues from DADLE-infused animals, the antisecretory dose-effect curves of the three enkephalin analogs displayed downward shifts to the right compared to control conditions. In contrast, the potency of DADLE was significantly increased in tissues from animals chronically infused with and rendered physically dependent upon fentanyl. The administration of the opioid antagonists naloxone, diprenorphine or the selective delta-opioid antagonist M 154, 129 produced no significant changes in short-circuit current of mucosal segments from either DADLE- or fentanyl-infused animals. Chronic administration of either DADLE or fentanyl did not significantly alter the effects of nonopioids, bombesin, somatostatin or epinephrine, on ion transport; however, the efficacy but not the potency of neurotensin in increasing short-circuit current was attenuated after chronic DADLE infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa. 298 70

The somatostatin analog D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-NH-CH(CH2OH)CHOHCH3 (SMS 201-995) displaces [3h[naloxone from its binding sites (IC50, 38 +/- 60 nM), being more than 200 times more potent than somatostatin. As measured by the difference between [3H]dihydromorphine, [3H][D-Ala2,D-Leu5]enkephalin, and (-)-[3H]bremazocine binding, SMS 201-995 appears to be highly specific for the opiate mu binding site. Electrophysiological data from hippocampal cultures and results from animal studies (tail flick, mydriasis) demonstrate the opiate antagonistic properties of SMS 201-995. SMS 201-995 is an opiate mu antagonist with a peptide structure. That this property is displayed by a somatostatin analog is somewhat unexpected.
 ...
PMID:Opiate antagonistic properties of an octapeptide somatostatin analog. 612 77

The distribution of neuropeptide Y, substance P, vasoactive intestinal polypeptide, Leu5-enkephalin, bombesin/gastrin-releasing peptide, calcitonin gene-related peptide, somatostatin, cholecystokinin and catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase was studied immunohistochemically in nerve fibres supplying the bovine vagina and uterus. The nerves containing tyrosine hydroxylase or dopamine-beta-hydroxylase and neuropeptide Y-immunoreactivity were particularly numerous in both organs. Substance P, vasoactive intestinal polypeptide and Leu5-enkephalin-containing nerves were less numerous whereas somatostatin and calcitonin gene-related peptide-immunoreactive nerves occurred occasionally. Bombesin/gastrin-releasing peptide and cholecystokinin immunoreactivities were not present in nervous fibers of the bovine uterus and vagina. Generally, the immunoreactive nerve terminals, fibers, networks or nerve bundles were present below the serous membrane, between smooth muscle cells of muscular layers, around blood vessels, in the submucosal layer and below the luminal epithelium of the uterus and cervix.
 ...
PMID:Peptidergic innervation of the bovine vagina and uterus. 777 Nov 84

Recent evidence supports the hypothesis of a direct action of LHRH at the level of the prostate. Since peptidases able to degrade the hormone are present in several LHRH target structures, it was deemed of interest to investigate whether the prostate of adult normal male rats might possess LHRH degrading activities (LHRH-DA). Through the use of RP-HPLC, it has been observed that LHRH-DA is present in the soluble fraction of the rat ventral prostate homogenate, and is able to hydrolyze synthetic LHRH and to generate fragments 1-3 and 1-5 of the decapeptide. The degradation of [pGlu-3H]LHRH is inhibited by LHRH itself, and affected by several LHRH agonists and antagonists with different kinetics and potencies. TRH, the enkephalin analog [D-Ala2-D-Leu5]enkephalin and rat prolactin do not inhibit the degradation of [pGlu-3H]LHRH by the soluble fraction of prostate homogenate; on the contrary, this is inhibited by graded doses of somatostatin. The prostatic LHRH-DA is also inhibited, in a dose dependent manner, by bacitracin, serine protease inhibitors (diisopropylfluorophosphate and phenylmethansulfonylfluoride), the metal chelating agent EDTA, HgCl2, and dithiothreitol. No inhibitory effect on [pGlu-3H]LHRH hydrolysis was observed after incubation of the prostatic extract in the presence of captopril. The prostatic LHRH-DA seems to be different from that present in other tissues of the rat (e.g., hypothalamus, pituitary, gonads), and to be decreased by castration performed 3 weeks before. These results suggest that (1) an LHRH-DA is found in the soluble fraction of rat prostate homogenate; (2) this enzymatic activity exhibits the characteristics of a metallo- and thiol-dependent neutral endopeptidase; (3) it appears to be different from similar hydrolytic activities found in other tissues; and (4) it is influenced by the hormonal milieu, since castration causes a significant decrease of its activity.
 ...
PMID:Characterization of a soluble LHRH-degrading activity in the rat ventral prostate. 825 44

The presence and pattern of coexistence of catecholamine-synthesizing enzymes and some neuropeptides in nerve fibres supplying thoraco-cranial arteries of the sexually immature gilts were investigated in whole mount preparations. The studied substances included: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H) (as markers of catecholaminergic nerve fibres), neuropeptide Y (NPY), Leu5-enkephalin (LENK), vasoactive intestinal polipeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), somatostatin (SOM) and serotonin (5-HT). The arteries were found to be richly supplied by TH/D beta H-immunoreactive (TH/D beta H) nerve fibers. Of the neuropeptides studied, NPY (rich innervation), LENK (moderate innervation), VIP (moderate innervation) and CGRP, SP, GAL (only a few nerve fibres) were detected in periarterial nerves. The following patterns of coexistence of the studied substances were found: TH+/D beta H+, TH+/D beta H+/NPY+, TH+/D beta H+/LENK+, TH-/D beta H-/NPY+, TH-/D beta H-/VIP+, TH+/D beta H+/VIP+ (only a few nerve fibres in the cerebral arteries), LENK+/NPY+, LENK-/NPY+, LENK+/NPY-. No SOM and 5-HT-positive structures were observed in the porcine blood vessels.
 ...
PMID:Immunohistochemical study of the existence and coexistence of catecholamine synthesizing enzymes and some neuropeptides in perivascular nerve fibres of the main thoraco-cranial arteries in the pig. 861 80

When the right vagus nerve of anesthetized cats was stimulated with repetitive bursts of pulses, decelerated heart rate became synchronized to the rhythm of the vagal bursts. Each burst applied to the vagus was followed by a single heart contraction. Within defined limits an increase in the frequency of vagal bursts evoked a proportional acceleration of the heart, whereas a decreased frequency diminished the heart rate. Therefore, over the range of synchronization the heart rate was precisely controlled by changing the vagal stimulation rate. We concluded that the chronotropic effect evoked by vagal bursts was composed of two functionally different types of influence, namely, inhibitory tonic and synchronizing. The vagotropic influence of intravenously injected regulatory peptides was found to be selective for either the tonic or synchronizing component. For instance, dalargin (D-Ala2-Leu5-Arg6-enkephalin) and neokyotorphin selectively diminished the inhibitory tonic vagal influence, whereas delta sleep inducing peptide and neurotensin potentiated it. The magnitude of synchronizing vagal influence was not modified by these peptides. In contrast, secretin selectively inhibited the synchronizing vagal effect, but the tonic one was not affected. Somatostatin potentiated the synchronizing effect but diminished the tonic one. These data support the hypothesis that certain regulatory peptides can modulate the effects of repetitive vagal bursts on pacemaker activity.
 ...
PMID:Regulatory peptides as modulators of vagal influence on cardiac rhythm. 874 72

In previous studies, we have shown that opioid agonists ([D-Ala2, D-Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reaction, also in the T47D human breast cancer cell line, of mu-acting opioids with type-II somatostatin receptors. Since a potential source of opioid activity in the breast might be casomorphin peptides (produced by the enzymatic degradation of alpha-casein and beta-casein), we investigated the antiproliferative action of five different casomorphin peptides: alpha-casein-(90-95), alpha-casein-(90-96), beta-casomorphin, beta-casomorphin-(1-5) and morphiceptin. We show that all five peptides decreased, in a dose-dependent manner, cell proliferation. The general antagonist diprenorphine produced only a partial reversal of their action. Furthermore, we provide evidence that all peptides (except for morphiceptin) bind to delta- and kappa-opioid binding sites of T47D cells with different selectivity. Finally, we show that these peptides are also partial competitors at the somatostatin receptors present in the same cell line.
 ...
PMID:Antiproliferative and receptor binding properties of alpha- and beta-casomorphins in the T47D human breast cancer cell line. 888 20

The presence of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H) and some neuropeptides, including neuropeptide Y (NPY), Leu5-enkephalin (LENK), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL) and somatostatin (SOM) was investigated in nerve fibres and perikarya of the median eminence-arcuate nucleus complex (MEARC) of the sexually immature female pigs by means of the immunohistochemical avidin-biotin complex method. Although immunoreactivities to all the studied substances were found in nerve fibres of the porcine MEARC, there were differences in the distribution and density of particular subsets of nerve fibres within the complex. While loose D beta H-immunoreactive (D beta H-IR) and dense TH-, NPY- and VIP-IR nerve meshworks occurred predominantly in the internal layer of the MEARC, nerve fibres immunoreactive to TH, CGRP, SOM, SP and LENK were more numerous in the external than in the internal layer of the median eminence (ME). Numerous TH-, D beta H-, NPY-, VIP-, SP- and CGRP-IR perivascular nerve fibres were also observed within both layers of the median eminence. There were also differences in the distribution of a particular subset of neurons within the porcine MEARC: NPY-, VIP-, GAL-, SP- and TH-IR (but not D beta H-IR) perikarya were found in the arcuate nucleus, while in the median eminence only subpopulations of NPY-, VIP and GAL-IR neurons were observed.
 ...
PMID:Distribution of catecholamine-synthesizing enzymes and some neuropeptides in the median eminence-arcuate nucleus complex (MEARC) of the immature female pig. 896 Mar 6

Double-labelling immunofluorescence was used to investigate the coexistence of the catecholamine-synthesising enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase and several neuropeptides including neuropeptide Y, vasoactive intestinal polypeptide, Leu5-enkephalin, somatostatin, calcitonin gene-related peptide and substance P in nerve fibres supplying the vas deferens in juvenile and adult pigs. The study has revealed three major populations of nerve terminals innervating the organ: (1) noradrenergic fibres; (2) non-noradrenergic (putative cholinergic) fibres containing vasoactive intestinal polypeptide, neuropeptide Y and somatostatin, supplying almost exclusively the lamina propria; and (3) non-noradrenergic, presumably sensory fibres, containing calcitonin gene-related peptide and substance P. The population of noradrenergic nerves can be divided into three subpopulations: a somatostatin-containing, a Leu5-enkephalin-containing and a subpopulation immunonegative to the peptides investigated, in descending order of magnitude. Coexistence patterns of the substances existing within nerve fibres supplying the vas deferens blood vessels are clearly different from those found in nerve fibres innervating the organ wall. The majority of the noradrenergic fibres associated with blood vessels contain neuropeptide Y only, while non-noradrenergic perivascular nerves contain predominantly vasoactive intestinal polypeptide. The possibility of different sources of origin of the particular nerve fibre subpopulations supplying the porcine vas deferens and its blood vessels is discussed.
 ...
PMID:Immunohistochemical characteristics of nerve fibres supplying the porcine vas deferens. A colocalisation study. 910 94


<< Previous 1 2 3 Next >>