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)

This article deals with the neuropeptides found in the eye and their actions. Substance P (SP) and VIP have been found in the anterior chamber of the eye. Here SP is localized in the sensory nerves of the sclera, cornea, iris, ciliary body and ciliary processes. It is supposed to be a sensory transmitter but can also be liberated by peripheral nerve endings as a response to various trauma. When this happens in the eye, for instance, after irritation of the Vth cranial nerve, SP causes an intense and long lasting miosis and may have some further actions as well. VIP has been demonstrated in nerves (probably cholinergic) of the posterior choroid and ciliary body. It is a potent vasodilator and may regulate choroideal blood flow. The retina is especially rich in different neuropeptides. SP, VIP, neurotensin, enkephalin, somatostatin, glucagon and gonadotropin-releasing hormone have all been demonstrated in the inner plexiform layer of the retina of various animal species. Specific information about the physiological role of retinal neuropeptides is still scarce but research is in progress. Considering the clinical significance of the new information about ocular neuropeptides, SP seems to be the most important substance. Recently a synthetic SP antagonist was reported to block the inflammatory response in the rabbit eye, which suggests a clinical use for this type of compounds.
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PMID:Ocular neuropeptides. 617 9

Inactivation of substance P and its C-terminal hexapeptide analog [p-Glu6]substance P6-11 was studied in rat parotid and hypothalamic slices. It was found that in the parotid slice system the decay of substance P induced K+ release occurs concurrently with a decrease in the biologically active concentration of the peptide in the medium. The inactivation was further studied using [p-Glu6]substance P6-11 as substrate in the parotid and in the hypothalamic slice systems. In both tissue preparations the hexapeptide is degraded to small peptide fragments by metalloendopeptidase. Separation of the peptide fragments by high performance liquid chromatography and determination of their amino acid composition showed that in the hypothalamic slice system the major cleavage of the hexapeptide analog occurs between Phe8-Gly9 with minor cleavage sites between Phe7-Phe8 and Gly9-Leu10. In the rat parotid slice system the major cleavage occurs between Gly9-Leu10 with a minor cleavage site between Phe7-Phe8. The degradation of the hexapeptide analog in the hypothalamic system was inhibited 77% and 67% by treatment with 1 mM p-chloromercuriphenylsulfonate and p-chloromercuribenzoate, respectively, whereas in the parotid system these reagents inhibited the degradation of the hexapeptide only by 15% and 8%. These results may indicate that different proteases in the parotid and hypothalamus are involved in degradation of substance P. Kinetic studies, including the use of various inhibitors as well as competition by the peptide hormones somatostatin, LHRH, TRH and Leu-enkephalin-NH2, revealed that in both tissues the hexapeptide analog is a preferred substrate for degradation by protease of considerable specificity towards the C-terminal sequence of substance P. It is suggested that this metalloendopeptidase may be important in the termination of the substance P response.
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PMID:Substance P degrading systems of rat parotid and hypothalamus. 620 Jan 41

The properties of gonadotropin-releasing hormone (GnRH) receptors were analyzed in isolated pituitary cells prepared by enzymatic dispersion with trypsin or collagenase-hyaluronidase. The initial impairment of LH responses to GnRH in isolated cells prepared by both methods was reversed during culture for 2 days in multiwell vessels. However, specific binding sites for GnRH, assayed by equilibration with [125I]iodi0[D-Ser(t-BU)6]des-Gly10-GnRH N-ethylamide (GnRH-A) were demonstrable in collagenase-dispersed cells, both initially and after 2 days in culture. Cellular uptake of GnRH-A was temperature dependent, with rapid and saturable binding to a limited number of specific receptor sites with high affinity for the labeled analog (Ka = 4.0 +/- 0.8 X 10(9) M-1). These sites showed common binding specificity for GnRH-A and the native GnRH peptide, with significantly lower affinity for the natural peptide (Ka = 2.3 X 10(7) M-1). Other protein and peptide hormones, including ovine LH, ovine PRL, hCG, TRH, somatostatin, and angiotensin II (up to 10(-6) M) did not inhibit binding of GnRH-A to its receptors. Cellular binding of GnRH-A was followed by increased cGMP production and LH release within 10 min. The analog was 50 times more potent than native GnRH in stimulating LH release. The Kact values derived for GnRH and GnRH-A were 0.5 and 0.01 nM, respectively, considerably lower than the Kd values of 50 and 0.25 nM derived from receptor binding analysis. These results indicate that GnRH receptors can be identified in isolated pituitary cells, in which peptide binding is followed by increased cGMP production and LH release. The impaired LH responses in acutely dispersed pituitary cells are not due to the loss of receptor sites but to a reversible postreceptor defect. Occupancy of about 20% of the GnRH-binding sites elicits a near-maximal LH response, indicating the nonlinearity of GnRH-receptor coupling to secretory responses in the cultured gonadotroph.
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PMID:Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. 625 Jul 93

Major advances in our understanding of the synthesis and release of anterior pituitary hormones have been made over the past several years. Neurons of the hypothalamus have been found to serve as "neuroendocrine transducers" in that they have both electrical and secretory functions. Peptidergic neurons respond to appropriate stimuli with a release of hypothalamic factors into the hypophyseal-portal system. These factors or hormones ultimately control the endocrine function of anterior pituitary cells. Three hormones, Thyrotropin Releasing Hormone (TRH), Gonadotropin Releasing Hormone (GnRH or LHRH) and somatostatin have been identified, synthesized and tested for clinical applications. The clinical assessment of pituitary function has been greatly improved by new and improved radioimmunoassays. One of the recent clinical advances in the area of pituitary disease has been the determination of the relatively high frequency of prolactinomas. Prolactin secreting microadenomas are an important and treatable cause of amenorrhea and infertility in young women. In addition, many pituitary tumors previously believed to be non-functional or "chromophobe adenomas" appear to be prolactinomas. Many new diagnostic and therapeutic techniques are continuing to be developed to improve our management of patients with hypothalamic-pituitary disease.
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PMID:Recent advances in the control and function of the anterior pituitary. 627 29

Homogenates of human luteal tissue bound radioiodinated luteinizing hormone releasing hormone agonist. Specific binding was both time- and temperature-dependent. Native LHRH and two LHRH agonists competed for binding, whereas TRH, somatostatin and oxytocin did not, indicating that the binding sites were specific. The apparent Ka values were 2 X 10(7)M-1 for both LHRH agonists and 10(6)M-1 for native LHRH. This is the first demonstration of specific binding of LHRH to human ovarian tissue. No binding could be detected to ovarian tissue from postmenopausal women.
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PMID:Specific binding of luteinizing hormone releasing hormone to human luteal tissue. 630 78

Modulation of ectopic human chorionic gonadotropin (hCG) secretion by a human nontrophoblastic ovarian papillary cystadenocarcinoma cell line maintained in monolayer culture was studied. Exposure of cells to methotrexate (MTX, 0.1 microM) significantly enhanced hormone secretion while actual cell replication was decreased. In contrast, exposure of cells to actinomycin D (25 pM) for 24 hr completely abolished hormone secretion and resulted in death of all cells. Exposure of the cells to hypothalamic peptides (thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin) did not alter hCG production. hCG secretion was stimulated after 24-hr incubation with dibutyryl cAMP (100 microM) and by prostaglandin F1 alpha (10 microM). Two separate mechanisms of modulation of ectopic hCG by these cells are possible: a cAMP-mediated stimulation independent of cell-growth kinetics after exposure to dibutyryl cAMP and prostaglandin F1 alpha, and a selective inhibition of DNA synthesis which results in slowing of cell replication and concomitant increase in hCG production per cell.
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PMID:Modulation of ectopic secretion of human chorionic gonadotropin by cultured ovarian adenocarcinoma cells. 630 19

The present experiments tested the ability of putative neurotransmitters and neuromodulators to regulate cyclic adenosine 3':5'-monophosphate (cAMP) levels in rat hippocampal slices. Slices from ovariectomized adult female rats were equilibrated for 1 hr and incubated for 20 min with various test compounds, and cAMP was extracted and quantified using a competitive protein-binding assay. Norepinephrine, adenosine, histamine, and prostaglandins E1 and E2 alpha, induced moderate (1.5- to 5-fold) increases in cellular cAMP, whereas dopamine, serotonin, prostaglandin F2 alpha, and glutamate were relatively ineffective. Most striking was the observation that vasoactive intestinal peptide (VIP) produced marked elevation (approximately 80-fold at 6 microM) of hippocampal slice cAMP content. In contrast, other peptides produced only 2-fold increased (glucagon, somatostatin) or no change in cellular cAMP levels (enkephalins, LHRH, ACTH analogue, arginine vasopressin). Significant elevations in cAMP were seen with VIP concentrations as low as 20 nM; the cAMP response was half-maximal at 1 microM VIP and maximized between 10 and 20 microM. At maximally effective concentrations, VIP was 86% as effective in increasing cAMP as maximal concentrations of forskolin, a compound which activates adenylate cyclase in most cell types. The cAMP response to 10 microM VIP was pronounced after a 1-min incubation (16-fold elevations) and was maximal at 30 min (140-fold elevation). When slices from other brain areas were compared, it was found that regions known to contain high levels of VIP (cerebral cortex) also responded to VIP treatment with 30- to 50-fold elevations in cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activators of cyclic adenosine 3':5'-monophosphate accumulation in rat hippocampal slices: action of vasoactive intestinal peptide (VIP). 631 11

Immunoreactive TRH (TRH-IR) in rat pituitary stalk blood and hypothalamus was investigated with high performance liquid chromatography in conjunction with a sensitive RIA. The TRH-IR of ethanol extracts of stalk blood resolved into three peaks, whether the blood was collected with the pituitary gland in situ or after the gland had been removed. The first peak corresponded to authentic TRH. By contrast, all the immunoreactive TRH in pituitary and hypothalamic extracts and in peripheral blood to which hypothalamic or synthetic TRH had been added eluted as a single peak with the same retention time as authentic TRH. The additional IR peaks in stalk blood did not correspond to known metabolites of TRH, and, since absent from the hypothalamus, they are unlikely to represent stored TRH precursors. Although authentic TRH constituted only 37% of total TRH-IR in pituitary stalk blood, the amount released during the first hour into stalk blood (1.7 ng) in relation to hypothalamic content (approximately 5 ng) was still high (approximately 34%) compared with that of LHRH (approximately 0.6%) and somatostatin (approximately 0.3%).
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PMID:Thyrotropin-releasing hormone in rat pituitary stalk blood and hypothalamus: studies with high performance liquid chromatography. 641 7

Hypothalmic tissue from 16 to 18-day fetal rats was transplanted onto the choridal pia overlying the superior colliculus in adult female rats. After survival periods of 2 weeks to 19 months, brains containing transplants were processed for monoamine fluorescence histochemistry, immunohistochemistry for three neuropeptides (LHRH, somatostatin, neurophysin), or for autoradiography in ovariectomized hosts that received [3 H] estradiol. Most of the transplants survived and retained or increased in size; 14 of 25 transplants examined by fluorescence histochemistry were found to contain median eminence-like structures. In almost all of the transplants that were stained for neuropeptides, beaded processes and occasional cell bodies were observed. Although immunoreactive fibers were found near blood vessels, no palisade arrangement typical of the normal median eminence was evident. Each of the hypothalamic transplants on which steroid autoradiography was performed contained clusters of estrophilic neurons, the intensity of labeling of which was comparable to that seen in the host hypothalamus. These results indicate that many characteristic morphological and chemical features of the hypothalamus, which are not evident in the 16 to 18-day fetus, are elaborated in transplants during the survival period in the host. Transplantation of fetal hypothalamus to adult choridal pia thus appears to be a valuable approach for studying the factors, humoral or neural, that regulate the differentiation of this brain region.
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PMID:Differentiation of embryonic hypothalamic transplants cultured on the choroidal pia in brains of adult rats. 698 85

In summary, highly vascularized CVOs of the mammalian brain are the site of increased vascular permeability for peptides and other molecules which generally do not cross the blood-brain barrier. In the CVOs the blood-brain barrier is shifted from the level of the capillaries to the tight junctions of the oligociliated ependymal cells. The neurohypophysis is the well known target of various peptidergic neuroendocrine neurons. In the neural lobe, peptide hormones from magnocellular neurons are stored and released into the general circulation in the median eminence, releasing and inhibiting hormones enter the hypothalamo-adenohypophyseal portal circulation. The OVLT appears to be an additional vascular outlet for LHRH and somatostatin. In the pineal, no pinealocytes stain positively for arginine-vasotocin; however, occasionally a single neurophysin (vasopressin or oxytocin) fiber has been observed. In the subfornical organ and area postrema which do not appear to have a primary neuroendocrine function, hemo-neural interactions may be important for effects of circulating peptides and other molecules on specific receptors. In the subcommissural organ, which does not have a special vascular permeability, ependymal cells secrete Reissner's fiber, a mucopolysaccharide, whose function in unclear.
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PMID:Relation of neuropeptides to mammalian circumventricular organs. 701 Sep 39


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