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)

After four decades of intense and competitive research, three hypothalamic releasing hormones (formerly factors) have recently been isolated and characterized. These are the decapeptide gonadotrophin releasing hormone (GnRH), tripeptide thyrotrophin releasing hormone (TRH), and the tetradecapeptide somatostatin. Some aspects of these hormones are discussed, and GnRH is considered in greater detail to demonstrate the difficulties involved in fulfilling completely the criteria which determine whether a substance can be accepted as a physiological releasing hormone. A substance immunologically similar to GnRH is present in rat hypophysial portal vessel blood, but, while the amount of this substance released into the portal circulation can be increased significantly by electrical stimulation of the preoptic area, no significant changes occur during the oestrous cycle or after long-term castration. This may be due to interference with the normal secretion of GnRH by the trauma and anaesthesia which necessarily accompany exposure of the pituitary stalk. However, the possibility exists that our preconceived notions regarding the changes in plasma levels of releasing hormones under physiological conditions may be incorrect. Thus it seems likely that changes in the rate of secretion of thyrotrophin is effected by throid hormones modulating the responsiveness of the thyrotrophs to a steady input of TRH. Evidence is presented for the existence of a similar mechanism for gonadotrophin secretion, and the role of steroid hormones and the priming effect of GnRH in modulating the responsiveness of the gonadotrophs is considered. The intrinsic connexions of the hypothalamus, the role of the hypothalamic aminergic systems and the autonomy of the hypothalamus with respect to anterior pituitary control present many problems which will prove difficult to solve.
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PMID:The development of the releasing factor concept. 2 35

Effects of intraventricular injection of sheep anti-somatostatin gamma-globulin (anti-SSG) on strychnine-induced seizures, strychnine LD50, and pentobarbital LD50 were examined in male rats under light ether anesthesia. Ten microliters of anti-SSG given 2 h earlier significantly decreased the duration of strychnine-induced seizures as compared with that in the control rats pretreated with normal sheep gamma-globulin (NSG). This effect of anti-SSG seemed to be specific, as there was no difference in seizure duration between sheep anti-LHRH gamma-globulin (anti-LHRHG)- and NSG-pretreated rats. Survival rates in anti-SSG-pretreated rats after injection of strychnine and pentobarbital were significantly larger (P less than 0.01 and P less than 0.05, respectively) than those in the control rats receiving NSG. The administration of anti-SSG resulted in 26.7% and 22.9% increases in the LD50 of strychnine and pentobarbital, respectively. These results indicate that endogenous somatostatin in the cerebrospinal fluids and/or the periventricular tissue nodulates the response of the central nervous system to strychnine and pentobarbital in rats.
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PMID:Effect of intraventricular administration of anti-somatostatin gamma-globulin on the lethal dose-50 of strychnine and pentobarbital in rats. 8 54

Intravenous infusion of somatostatin in mongrel dogs caused a significant decrease in the peripheral plasma renin activity (PRA) enhanced by pentobarbital sodium anesthesia or furosemide treatment. However, the inhibitory activity vanished within 10 min after termination of somatostatin infusion. Intrarenal arterial infusion of somatostatin decreased furosemide-enhanced PRA in renal vein by 24.0%, 16.6% and 8.6% in dose of 0.1, 0.5 and 1.0 microgram, respectively. On the other hand, high doses of the peptide (50-200 microgram) failed to decrease. The changes in PRA occurred in the absence of any alteration in blood pressure during the intravenous infusion under furosemide treatment. In an in vitro study, the addition of somatostatin in doses of 0.01 and 0.05 microgram suppressed the renin release in dog renal cortical cell suspension by 74.3% and 53.6%, respectively. Therefore, in both intrarenal arterial infusion and the cell suspension system, somatostatin was increasingly effective in decreasing renin release towards the lower end of the dose range tested. These results suggest that the effect of somatostatin on hyperreninemia may involve an inhibition of renin release at the cell level in the kidney.
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PMID:Effect of somatostatin on plasma renin activity. 47 26

Pulsatile GH secretion decreases during food-deprivation in the rat. It has been hypothesized that this decrease is due to elevated hypothalamic somatostatin secretion. This is based on the observation that GH increases in food-deprived rats following removal of endogenous somatostatin using passive immunization techniques. Cognizant of the important stimulatory effects of growth hormone-releasing hormone (GHRH) on GH secretion, we sought to determine if this neuropeptide plays any role in mediating GH secretion in food-deprived rats. Male rats were prepared with indwelling venous catheters using sodium pentobarbital anesthesia seven days prior to experimentation. Animals were food-deprived for 72 h, after which control blood samples were drawn from -60 to 0 min. One group was then treated with normal rabbit serum (NRS), while a second group was treated with GHRH antiserum (GHRHab). At 55 min all animals received somatostatin antiserum (SSab). No animal exhibited any spontaneous GH peak during the one hour control period or in the subsequent one hour period following the administration of GHRHab or NRS. Absence of GH pulsatility during food-deprivation, coupled with no decrease in GH levels in food-deprived rats treated with GHRHab suggest that diminished GHRH pulsatility is likely during food-deprivation. Subsequent treatment of these animals with SSab resulted in an identical 2.5 fold increase in GH concentrations. This result suggests that GHRH is not involved in the GH rebound following somatostatin withdrawal in food-deprived rats.
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PMID:Effects of passive immunization of growth hormone-releasing hormone and somatostatin on growth hormone secretion under conditions of high somatostatin tone. 134 4

Chronic hypoxic pulmonary hypertension (PH), associated with increased pulmonary arterial pressure (PPA) and right ventricular hypertrophy (RVH), correlates significantly with calcitonin gene-related peptide (CGRP) and somatostatin (SOM) levels in lung and blood. CGRP's role in regulation of PPA in chronic hypoxia and its potential interactions with SOM were investigated. CGRP, its antibody (ab) and blocker, CGRP-(8-37), SOM-14, SOM-28, and SOM-ab, respectively, were infused into the pulmonary circulation of hypobaric hypoxia rats for 4, 8, and 16 days. Thereafter, under pentobarbital sodium anesthesia, PPA was measured in the right ventricle and main pulmonary artery. Chronic CGRP infusion prevented PH at all times, whereas immunoneutralization and receptor blocking exacerbated PH. SOM-28 also exacerbated while SOM-14 and SOM-ab decreased PH. RVH generally reflected the PPA. Radioimmunoassay confirmed successful infusion of the peptides with negligible peptide degradation in the pumps throughout 16 days and showed complete immunoneutralization of CGRP with its ab. Peptide levels in lung tissue suggest inhibition of CGRP release by SOM-28 and increased plasma SOM with CGRP infusion. In vitro pharmacological studies suggest that CGRP exerts a receptor-mediated nonadrenergic, nonmuscarinic vasodilatory effect in the lung which is independent of endothelium-derived relaxing factor and does not involve ATP-dependent potassium channels. We conclude that endogenous CGRP plays an important role in pulmonary pressure homeostasis during hypoxia, by directly dilating pulmonary vasculature, thus ameliorating the development of chronic hypoxic pulmonary hypertension in rats.
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PMID:CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension. 135 80

The purpose of this study was to determine the heart rate and arterial blood pressure changes to isometric skeletal muscle contraction and muscle stretch before and after microinjecting an antagonist to substance P (SP) or somatostatin (SOM) into the L-7 dorsal horn region of the spinal cord of anesthetized cats. Anesthesia was induced by administering an anesthetic gas mixture and was subsequently maintained with alpha-chloralose. Triceps surae contraction was induced by electrically stimulating the L-7 ventral root. Three muscle manipulations (all 1 minute in duration) were performed: 1) continuous tetanic contraction, 2) intermittent tetanic contractions (1 second of contraction, 1 second of relaxation), and 3) passive muscle stretch. Saline microinjections had no effect on the cardiovascular responses to these muscle manipulations. However, both peptide antagonists blunted the pressor response to a continuous tetanic contraction as mean arterial pressure increased 47 +/- 4 and 44 +/- 4 mm Hg before and 28 +/- 3 and 28 +/- 4 mm Hg after microinjecting the SP or SOM antagonist, respectively. In contrast, neither antagonist influenced the increase in mean arterial pressure produced by passive stretch; values were 43 +/- 6 versus 41 +/- 6 mm Hg (SP antagonist) and 39 +/- 7 versus 42 +/- 7 mm Hg (SOM antagonist) before and after injections, respectively. Microinjecting the SOM antagonist attenuated the pressor response to intermittent tetanic contractions (44 +/- 4 mm Hg before SOM antagonist versus 26 +/- 4 mm Hg after SOM antagonist), whereas the SP antagonist had no effect (35 +/- 3 mm Hg before SP antagonist versus 32 +/- 4 mm Hg after SP antagonist).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of spinal microinjections of an antagonist to substance P or somatostatin on the exercise pressor reflex. 137 Sep 23

The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 micrograms/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthetized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthetized with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under these conditions in anesthetized rats.
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PMID:Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin. 167 Dec 92

The colchicine-induced accumulation of vasopressin (AVP) and oxytocin (OXT) has recently been applied to estimate the synthesis and turnover rates for these neuropeptides in whole rat hypothalamus. In the present studies, this pharmacologic procedure has been examined as a potential method for estimating hypothalamic somatostatin (SRIF) synthesis rate, and evaluated further for its utility in estimating nonapeptide synthesis in individual hypothalamic nuclei. Adult male rats received a single injection of colchicine (8 micrograms) into the third ventricle under pentobarbital anesthesia. Twenty-four hr later, immunoreactive (IR) levels of AVP and OXT increased considerably, as previously noted. Hypothalamic IR-SRIF levels, however, were unaffected. The absolute increases in IR-AVP and IR-OXT were greatest in the supraoptic nucleus (SON), with smaller increments in the para/periventricular hypothalamus (PVH) and the median eminence (ME). IR-SRIF levels showed no changes in the PVH or the ME. As a test, the method was applied to the detection of changes in AVP synthesis in diabetic rats. The colchicine procedure reported increases in AVP synthesis in both the SON and PVH in diabetic animals, a result compatible with that obtained previously for whole hypothalamus using radiolabeled procedures. Together, the results indicate that the colchicine procedure is useful in detecting changes in the syntheses of some (AVP and OXT) but not all (SRIF) neuropeptides, and that when applicable, the method is sufficiently sensitive to detect changes in small hypothalamic regions. The method may prove useful in estimating changes in peptide synthesis analogous to that used for serotonin and dopamine; e.g., 5-hydroxytryptophan and dopa accumulation following inhibition of aromatic L-amino acid decarboxylase.
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PMID:Colchicine-induced increases in immunoreactive neuropeptide levels in hypothalamus: use as an index of biosynthesis. 167 40

Better understood in other tissues, the effects of adenosine on insulin-stimulated glucose uptake in the heart are poorly understood. Under pentobarbital anesthesia, we instrumented mongrel dogs to obtain general hemodynamics (blood pressure and heart rate), and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of substrate uptake by the heart (Fick principle). Somatostatin (SRIF) was infused intravenously (0.8 micrograms/kg/min) along with 0, 0.5, 1.0, 5.0, or 10 mU/kg/min regular insulin, and variable quantities of glucose to maintain euglycemia. Concomitant with the SRIF, insulin, and glucose infusions, adenosine was infused in logarithmically increasing rates (0, 0.01, 0.1, 1.0, 10 or 100 mumol/min) for 30 minutes each into the main left coronary arteries. Insulin infusions increased myocardial glucose uptake in a dose-dependent manner. The heart displayed exquisite sensitivity to insulin, with an ED50 of approximately 14 microU/mL (serum insulin). Adenosine infusions in the absence of insulin (SRIF infusion) increased coronary blood flow, but did not alter myocardial glucose uptake. In the presence of insulin, adenosine increased the maximal value for glucose uptake without changing sensitivity to insulin. These results indicate that adenosine enhances myocardial responsiveness to insulin, with respect to glucose uptake, independent of changes in blood flow. Since glucose can be used for anaerobic metabolism, and adenosine levels are known to increase under situations in which myocardial oxygenation is inadequate, these data have serious implications for conditions such as myocardial ischemia or hypoxia, when glycolytic substrate availability is vital.
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PMID:Adenosine enhances myocardial glucose uptake only in the presence of insulin. 168 Feb 14

Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0.85 mg; medium dose, 1.7 mg; high dose, 3.4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 microgram human GHRH(1-29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506.0 +/- 68.5 micrograms/l), peak GH levels were enhanced by the low dose (704.4 +/- 47.8 micrograms/l, P less than 0.05), unaltered by the medium dose (543 +/- 65.8 micrograms/l) and suppressed by the high dose (312.7 +/- 55.2 micrograms/l, P less than 0.05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P less than 0.01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00-12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30-14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 microgram human GHRH(1-29) with samples taken at 5, 10, 20 and 40 min following stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat. 168 88


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