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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms involved in inhibition of insulin secretion by somatostatin and noradrenaline were compared in order to establish whether the receptors for these agents are coupled to similar effector systems in the pancreatic B cell. Both agents significantly reduced forskolin-induced adenylate cyclase activity in islet homogenates, although noradrenaline was more effective than somatostatin. The capacity of noradrenaline to inhibit insulin secretion was largely unaffected by agents that increase intracellular cyclic AMP, whereas the effect of somatostatin as an inhibitor was markedly reduced under these conditions. Both noradrenaline and somatostatin inhibited the stimulation of insulin secretion induced by K+ depolarization, but different mechanism were involved. Somatostatin significantly inhibited K(+)-stimulated 45Ca2+ efflux and influx in islets, while noradrenaline exerted only a minor influence on these processes. The data indicate that noradrenaline controls insulin secretion by a mechanism which operates beyond the level of intracellular messenger generation. In contrast, somatostatin exerts at least part of its inhibitory effect on insulin secretion by directly controlling islet cell Ca2+ influx in a manner which may be regulated by cyclic AMP.
J Mol Endocrinol 1990 Jun
PMID:Evidence for differential effects of noradrenaline and somatostatin on intracellular messenger systems in rat islets of Langerhans. 197 36

Bronchial reactivity changes during childhood, indicating possible changes in neural control. Nerves supplying the intrapulmonary airways were therefore studied in autopsy tissue from 14 normal infants (0 to 3.5 yr), 3 children (8.3 to 10.75 yr), and 4 adults (17 to 24 yr). An indirect immunofluorescence technique was used to study the distribution and relative number of nerve fibers containing the general neuronal markers protein gene product 9.5 and synaptophysin. Nerve subpopulations were identified using antisera to neuropeptide tyrosine, vasoactive intestine polypeptide, somatostatin, substance P, calcitonin gene-related peptide, and the enzyme tyrosine hydroxylase. Between birth and 3 yr, the distribution and relative number of immunoreactive nerves shown by both the general neuronal markers and specific antisera did not change. Neuropeptide tyrosine-immunoreactive nerves were the most common peptide-containing nerve subpopulation identified in the human lung, supplying bronchial smooth muscle, submucosal glands, cartilage, and submucosa. Other peptide-containing nerves exhibited distinct distribution patterns. Two differences in the airway innervation were identified between cases aged 0 to 3.5 yr and the older age groups. Relatively fewer peptide-containing nerves occurred in the adult bronchioli and respiratory unit, but the relative number of vasoactive intestinal polypeptide-containing nerves supplying the bronchial and bronchiolar smooth muscle was greater in the two older age groups. Given these apparent age-related differences in the number of peptide-containing nerves supplying the human airway, studies on the development of peptide receptors are indicated.
Am J Respir Cell Mol Biol 1990 Sep
PMID:Immunohistochemical localization of peptide-containing nerves in human airways: age-related changes. 197 91

Suramin is a polyanionic compound which has been used in the treatment of trypanosomiasis and acquired immunodeficiency syndrome (AIDS), while preliminary success has been reported in the treatment of cancer. However, suramin also causes adrenal insufficiency. We have previously reported that suramin selectively inhibited corticotropin (ACTH)-stimulated corticosterone release by dispersed adrenal cells in a dose-dependent manner via a direct interaction with the ACTH molecule. The present study was undertaken in order to investigate the effect of suramin on hormone release by dispersed rat anterior pituitary cells. Suramin at a concentration of 100 microM inhibited both basal and secretagogue-stimulated ACTH release by cells cultured in minimal essential medium (MEM) only, while it had no effect on ACTH release by cells cultured in MEM + 10% fetal calf serum (FCS) or MEM + 0.1% bovine serum albumin (BSA). In addition, suramin also caused a parallel decrease of prolactin (PRL) and growth hormone (GH) release by cells cultured in MEM only, suggesting a toxic, rather than a selective effect of suramin on anterior pituitary cells cultured in MEM only. In addition, suramin potentiated the effect of thyrotropin-releasing hormone (TRH) on PRL release by cells cultured in MEM + 10% FCS and suppressed the inhibitory effect of dopamine (DA) on PRL release by cells cultured in MEM + 10% FCS and in MEM + 0.1% BSA. Comparable suppressive effects of suramin on growth hormone-releasing hormone (GHRH)-stimulated and somatostatin (SRIH)-inhibited GH release were found in cells cultured in MEM + 0.1% BSA but not in cells cultured in MEM + 10% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1990 Aug 20
PMID:Effects of suramin on hormone release by cultured rat anterior pituitary cells. 198 Aug 98

Many clinical approaches for the treatment of hormone-sensitive tumors are being developed based on analogs of LH-RH and somatostatin. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of LH-RH agonists like [D-Trp6]-LH-RH and new LH-RH antagonists free of edematogenic effects such as [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10]-LH -RH (SB-75). Agonists and antagonists of LH-RH have been used in patients with prostate cancer and might be also beneficial for the treatment of breast cancer and ovarian, endometrial and pancreatic carcinomas. Some of the effects of LH-RH analogs can be due to direct action since LH-RH receptors have been found in these cancers. The use of sustained delivery systems based on microcapsules of PLG, makes the treatment more efficacious. Octapeptide analogs of somatostatin such as D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for antitumor activity. These somatostatin analogs, by virtue of having a wide spectrum of activities appear to inhibit various tumors through multiple mechanisms. Direct antiproliferative actions of somatostatin analogs appear to be mediated by specific receptors located on tumor cells. High affinity binding sites for RC-160 and related analogs have been found in human pancreatic, prostate, breast and ovarian cancers and brain tumors such as meningiomas. In vivo administration of analog RC-160 inhibits the growth of Dunning R-3327 prostate cancers in rats, MXT mammary tumors in mice and BOP-induced ductal pancreatic cancers in hamsters. Combination of microcapsules of RC-160 with [D-Trp6]-LH-RH results in synergistic potentiation of the inhibition of these cancers. Somatostatin analog RC-160 and LH-RH antagonist SB-75 are the object of further experimental studies and clinical trials aimed at the exploration of their inhibitory effects on the processes of malignant growth.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical studies. 198 Oct 9

High affinity somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SS-R were found in most tumors originating from SS target tissues, i.e. GH- and TSH-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors (including metastases) and brain tumors, including gliomas and neuroblastomas. SS-R were also expressed in several tumors originating from various other tissues, i.e. breast and small cell lung carcinomas, some colorectal cancers, and medullary thyroid carcinomas. In general, most of the SS-R+ tumors are well-differentiated and/or have neuroendocrine features. They often have low or absent epidermal growth factor receptor (EGF-R) expression. In some tumors (i.e. breast tumors) SS-R are not homogeneously distributed, making SS-R autoradiography a particularly useful tool for assessing SS-R status. SS-R are functional in pituitary and GEP tumors where they mediate hormone secretion inhibition. In these and in the other SS-R+ tumors, SS-R may also mediate antiproliferative effects of SS, as evidenced in animals where growth of SS-R+ tumor xenografts is inhibited by SS analogs. For diagnosis, SS-R+ tumors and metastases can be localized in vivo by scanning techniques after 123I-labelled SS analog injection.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Somatostatin receptors in malignant tissues. 198 Oct 10

This paper presents the results of the visualization of somatostatin (SS) receptor positive tumors in man after the i.v. administration of the SS analog Tyr3-octreotide coupled to 123I. It is an easy, quick and harmless procedure which allows imaging of primary and (often unexpected) secondary deposits and/or multiple localizations of the majority of endocrine pancreatic tumors, metastatic carcinoids and pituitary tumors, as well as of a multitude of tumors with neuroendocrine characteristics and well-differentiated brain tumors and meningiomas. In the case of hormone-secreting tumors a positive scan in most instances also predicts the subsequent successful therapy with octreotide.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Somatostatin receptor imaging in vivo localization of tumors with a radiolabeled somatostatin analog. 198 Oct 11

Newly developed somatostatin analogues may be useful agents in the treatment of breast and prostate cancer. Potential mechanisms of antitumor action include suppression of circulating levels of trophic hormones and growth factors as well as direct effects at the tumor level, potentially involving autocrine/paracrine mechanisms. Pilot clinical trials conducted in heavily pretreated women with advanced breast cancer indicate that SMS 201-995 (Sandostatin R) has minimal toxicity and moderately suppresses stimulated growth hormone secretion and basal somatomedin-C level. Somatostatin analogues have also been found to retard the growth of experimental prostate cancer, particularly when used in combination with LHRH analogues. The therapeutic efficacy of these compounds used alone or in combination with other agents in the treatment of breast and prostate cancer remains to be established in larger clinical trials involving less heavily pretreated patients.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Somatostatin analogues in the treatment of breast and prostate cancer. 198 Oct 12

Forty-nine primary breast tumors were analyzed for the expression of the somatostatin receptor (SSR) and genetic changes in the RB tumor suppressor gene. Twenty-four tumor samples were shown to contain receptors for somatostatin and in eight of these SSR-positive tumors we observed a mutation in the RB gene. However, since also in the group of SSR-negative tumors in eight of the 25 cases an alteration of the RB gene was observed, loss of this tumor suppressor gene is not specific for the SSR-positive subgroup of breast tumors. A similar, equal distribution between SSR-positive and SSR-negative breast tumors was observed for the six tumor samples which showed amplification of the neu proto-oncogene.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Genetic changes in somatostatin receptor positive breast tumors. 198 Oct 16

D2 dopamine receptors and somatostatin receptors in adenohypophyseal cells are coupled through G proteins to various transduction mechanisms. To study the involvement of these different transduction mechanisms and of various G proteins in the dopamine and somatostatin regulation of prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, we have pretreated the adenohypophyseal cells in primary culture with increasing doses of pertussis toxin. The guanosine triphosphate (GTP) dependency of the negative coupling of dopamine and somatostatin receptors with adenylate cyclase in the same membrane preparation from anterior pituitary cells was different. In fact, higher GTP doses were requested to obtain dopamine inhibition, suggesting that different G proteins were involved in the coupling of these two receptors with adenylate cyclase. However, the inhibition of adenylate cyclase activity by both neurohormones was fully sensitive to pertussis toxin pretreatment with a similar IC50 for the toxin. The IC50 for the toxin was also similar for the blockade of dopamine or somatostatin inhibition of the three-hormone secretion as well as for the stimulation on basal PRL or GH secretion or the reduction of thyrotropin-releasing hormone (TRH)-stimulated prolactin secretion, suggesting that the toxin acts through similar mechanisms on these different phenomena. Pretreatment of the cells with Bordetella pertussis toxin differentially affected the effects of both neurohormones on the three cell types. A complete reversion of the inhibition of secretion was observed only in the case of somatostatin on PRL and TSH cells. In contrast, the somatostatin inhibition of GH secretion was only partially reversed by the pertussis toxin pretreatment. This was also the case of dopamine inhibition of PRL secretion. It can be concluded that: (1) On PRL secretion dopamine and somatostatin do not share all the mechanisms since the intensity of their inhibition and the reversibility of their effects by pertussis toxin were differential. (2) Different mechanisms of action are implicated in the effect of somatostatin on PRL, GH and TSH secretions. (3) Different G proteins might be involved in the coupling of dopamine and somatostatin receptors with adenylate cyclase.
Mol Cell Endocrinol 1990 Oct 01
PMID:Differential coupling with pertussis toxin-sensitive G proteins of dopamine and somatostatin receptors involved in regulation of adenohypophyseal secretion. 198 65

Islet amyloid polypeptide (IAPP) in the pancreas of the spontaneously diabetic (BB) Wistar rat was examined by radioimmunoassay, and IAPP mRNA levels were determined by Northern blotting. IAPP-like immunoreactivity in the diabetic rat pancreas was found to be significantly depleted compared with control (non-diabetic) BB rats (85.9 +/- 5 pmol/g in control rats, n = 8, vs 8.97 +/- 0.9 pmol/g in diabetic rats, n = 5; mean +/- S.E.M.). A similar change in insulin concentrations was found, although insulin was present in approximately 100-fold greater amounts than IAPP. Chromatography of the IAPP immunoreactivity revealed a single molecular form, corresponding to synthetic IAPP. Northern blot analysis of pancreatic RNA (n = 4) revealed that IAPP mRNA in the diabetic group was depleted to 22% of the signal intensity in the control group. Insulin mRNA was dramatically reduced to only 4% of the control group and, in contrast, somatostatin was relatively unaffected, with the diabetic group retaining 86% of signal compared with the controls. This animal model of insulin-dependent diabetes results from severe autoimmune destruction of the beta cell. The extremely low levels of both insulin and its messenger RNA are in agreement with this. These results demonstrate that this pathological state is also associated with a loss of IAPP from the pancreas. Insulin-dependent diabetes is associated with a range of metabolic disturbances. It is possible that the concomitant depletion of IAPP may be a contributory factor in exacerbating the condition.
J Mol Endocrinol 1991 Feb
PMID:Depletion of islet amyloid polypeptide in the spontaneously diabetic (BB) Wistar rat. 201 54


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