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

We determined the effects on nociceptive threshold and motor function of dynorphin-gene products, dynorphin A-(1-32) (DYN A-(1-32), DYN A-(1-8), DYN B and DYN B-29 and the non-opioid peptides somatostatin, neurotensin and salmon calcitonin (s-CT) after intrathecal administration in the rat. DYN A-(1-32) (25 nmol) produced maximal elevation of tail-flick latency accompanied by severe hind limb paralysis and tail flaccidity lasting 6 h and still present at 24 h in several animals. Antinociception evaluated by the vocalization test wore off within 2 h. A lower dose of the peptide (6.25 nmol) did not alter the tail-flick reflex and motor function but significantly elevated the vocalization threshold. The other dynorphins showed weaker, short-lasting activity on the nociceptive threshold, the order of potency being as follows: DYN B-29 greater than DYN B greater than DYN A-(1-8). On the other hand, at the high doses DYN B (100 nmol) and DYN B-29 (50 and 100 nmol) caused moderately severe hind limb paralysis whereas DYN A-(1-8) did not cause any motor impairment up to the dose of 100 nmol. MR 1452, a relatively preferential antagonist of the kappa opioid receptor, prevented both the antinociceptive and motor effects of dynorphins. Intrathecal somatostatin (25 nmol) had a profile of activity superimposable on that of DYN A-(1-32): long-lasting (up to 24 h) elevation of tail-flick latency with hind limb paralysis, and a shorter (4 h) elevation of the vocalization threshold. MR 1452 did not modify these effects. Intrathecal neurotensin (25 nmol) and s-CT (0.5 nmol) did not alter tail-flick latency or vocalization threshold. However, adopting the hot plate as the analgesimetric test, both peptides elevated the time of hind paw licking, taken as an index of nociception. No signs of motor dysfunction were observed at the doses employed.
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PMID:Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat. 290 71

While trying to identify new members of the somatostatin receptor family of G protein-coupled receptors, we isolated cDNAs from a mouse brain library encoding two related receptor-like proteins, designated msl-1 and msl-2, of 380 and 372 amino acids, respectively. There was 61% identity and 71% similarity between the sequences of msl-1 and msl-2. Among members of the G protein-coupled receptor superfamily, the sequences of both msl-1 and msl-1 were most closely related to those of the somatostatin receptors (SSTRs), having approximately 35% identity with the sequence of SSTR1. Transient expression in COS-1 cells showed that msl-1 and msl-2 did not bind somatostatin. Rather they bound opioids selectively and with high affinity and had the pharmacological properties of kappa and delta opioid receptors, respectively. Indeed, the sequence of msl-2 was identical to that of a delta opioid receptor recently cloned by other workers. Functional characterization of kappa/msl-1 and delta/msl-2 opioid receptors showed that they were coupled to G proteins and mediated opioid receptor class-specific agonist inhibition of forskolin-stimulated cAMP formation. RNA blotting studies and in situ hybridization histochemistry showed that kappa opioid receptor mRNA was expressed at high levels in brain in the neocortex, hippocampus, amygdala, medial habenula, hypothalamus (arcuate and paraventricular nuclei), locus ceruleus, and parabrachial nucleus, suggesting that this receptor may play a role in arousal and regulation of autonomic and neuroendocrine functions.
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PMID:Cloning and functional comparison of kappa and delta opioid receptors from mouse brain. 839 75

Somatostatin and opioid systems, are the two main inhibitory systems in mammals. Both classes of substances have been identified in normal and malignant mammary gland, as well as their cognitive receptors. They have been implied in the inhibition of cell growth of cancer cells and cell lines, in a dose-dependent and reversible manner. Somatostatin acts through homologous receptors (SSTRs), belonging to five distinct classes (SSTR1-5). We, and others have identified SSTR2 and 3 as been the only SSTRs present in the breast. Furthermore, opioids act through the three classes of opioid receptors (mu, delta,kappa). In the breast, kappa opioid receptor subtypes (kappa 1-kappa 3) are the most widely expressed. We further have shown that opioids, in addition to their binding to opioid receptors, compete for binding to SSTRs. This functional interaction, together with other identified modes of opioid action in the breast (modulation of steroid receptors, proteases' secretion, interaction with cytoskeletal elements), will be discussed, taking into consideration also the possible local production of casomorphins (casein-derived opioids), which are very potent antiproliferative agents.
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PMID:Somatostatin and opioid receptors in mammary tissue. Role in cancer cell growth. 1095 9

In our previous studies (J. Chem. Neuroanat. 2000;19:233-241), kappa opioid receptors were immunocytochemically identified in inhibitory interneurons of the dentate hilus and CA1 area of the rat hippocampus. From among the known interneuron subtypes, somatostatin- (SOM) and neuropeptide Y- (NPY) immunoreactive (IR) hippocampal interneurons show morphology and distribution similar to the kappa opioid receptor (KOR) immunopositive cells. In the present study, with the help of double immunocytochemical labelling, we provide direct evidence that the majority of the interneurons immunoreactive for SOM and/or NPY also express the kappa opioid receptor. The receptor was localized on the perikaryal and proximal dendritic region of the SOM- and NPY-immunopositive neurons in the dentate hilus and the CA1 region. From among the SOM-immunoreactive cells, 77% in the dentate hilus and 51% in the CA1 stratum oriens was double labelled. In the case of NPY-immunoreactive neurons this proportion was 56 and 65%, respectively. The co-expression of KOR and SOM/NPY suggests that hippocampal interneurons can selectively be activated by the different opioids under different physiological circumstances.
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PMID:Kappa opioid receptor is expressed by somatostatin- and neuropeptide Y-containing interneurons in the rat hippocampus. 1189 88

There are several lines of evidence that indicate a prominent role for the opioid system in the acquisition and consolidation of learned associations. Specifically, kappa opioid receptor (KOR) modulation has been demonstrated to alter various behavioral tasks including whisker trace eyeblink conditioning (WTEB). WTEB is an associative conditioning paradigm in which a neutral conditioned stimulus (CS; Whisker stimulation) is paired following a short stimulus free trace interval with a salient unconditioned stimulus that elicits a blink response (US; Eye shock). Work from our laboratory has shown that WTEB conditioning is dependent upon and induces plasticity in primary somatosensory cortex (S1), a likely site for memory storage. Our subsequent studies have shown that WTEB acquisition or consolidation are impaired when the initial or later phase of KOR activation in S1 is respectively blocked. Interestingly, this mechanism by which KOR is activated in S1 during learning remains unexplored. Dynorphin (DYN), KOR's endogenous ligand, is synthesized from the precursor prodynorphin (PD) that is synthesized from preprodynorphin (PPD). In S1, most PPD is found in inhibitory GABAergic somatostatin interneurons (SOM), suggesting that these SOM interneurons are upstream regulators of learning induced KOR activation. Using immunofluorescence to investigate the expression of PD and SOM, the current study found that PD/SOM expression was transiently increased in S1 during learning. Interestingly, these findings have direct implications towards a time- and learning-dependent role for KOR activation in neocortical mechanisms mediating learning.
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PMID:Neocortical prodynorphin expression is transiently increased with learning: Implications for time- and learning-dependent neocortical kappa opioid receptor activation. 2880 36