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)

The effect of haloperidol, a dopaminergic antagonist, on insulin and glucagon secretion was investigated using the isolated, perfused canine pancreas. Haloperidol at 4 X 10(-7) to 10(-5) mol/l caused a dose-dependent inhibition of glucagon release both at low (25 mg/100 ml) and high glucose concentrations (150 mg/100 ml). At the low glucose concentration insulin release was already maximally suppressed. At the high glucose concentration haloperidol (4 X 10(-7) to 10(-5) mol/1) also caused a dose-dependent inhibition of insulin release. Haloperidol (10(-5) mol/1) inhibited dramatically pancreatic A and B cell responses to isoproterenol (2 ng/ml), acetylcholine (1 mumol/1) and arginine (5 mmol/1). The inhibitory effect of haloperidol on both glucagon and insulin release could be eliminated by increasing perfusate calcium concentration from 1.3 to 8.8 mmol/1. These findings suggested that haloperidol blocks glucagon and insulin release in a somatostatin-like manner by affecting a fundamental step of the stimulus-secretion coupling, probably by interfering with calcium handling of the pancreatic A and B cells.
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PMID:Haloperidol, a dopaminergic antagonist: somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas. 71 Jul 56

Control of growth hormone (GH) and prolactin (PRL) release was investigated in hypophysial stalk-transected (HST) and stalk-intact pigs by determining the effects of analogs of GH-releasing factors (GHRF), somatostatin (SRIF), arginine, thyrotropin-releasing hormone, alpha-methyl-rho-tyrosine, and haloperidol. HST and control gilts were challenged with intravenous injections of human pancreatic GHRF(1-40)OH, thyrotropin-releasing hormone, and analogs of rat hypothalamic GHRF. HST animals remained acutely responsive to GHRF by releasing 2-fold greater quantities of GH than seen in controls. This occurred in spite of a 38% reduction in pituitary gland weight and a 32 and 55% decrease in GH concentration and total content. During SRIF infusion, GH remained at similar basal concentrations in HST and control gilts, but increased immediately after stopping SRIF infusion only in the controls. Releasable pituitary GH appears to accumulate during SRIF infusion. GHRF given during SRIF infusion caused a 2-fold greater release of GH than seen in animals receiving only GHRF. Arginine increased (P less than 0.05) GH release in controls, but not in HST gilts, which suggests that it acts through the central nervous system. Basal PRL concentrations were greater (P less than 0.05) in HST gilts than in control gilts. TRH acutely elevated circulating PRL (P less than 0.001) in HST gilts, suggesting that it acts directly on the pituitary gland. Haloperidol, a dopamine receptor antagonist, increased circulating PRL in controls but not in HST animals. alpha-Methyl-rho-tyrosine did not consistently increase circulating PRL, however, suggesting that it did not sufficiently alter turnover rate of the tyrosine hydroxylase pool. The results indicate that the isolated pituitary after HST remains acutely responsive to hypothalamic releasing and inhibiting factors for both GH and PRL release in the pig.
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PMID:Growth hormone and prolactin secretion in hypophysial stalk-transected pigs as affected by growth hormone and prolactin-releasing and inhibiting factors. 167 Dec 98

TRH is present in human normal pituitaries and in pituitary adenomas. In this study we demonstrated that the same tissues can release TRH in vitro. Fragments from seven normal pituitaries (10-15 mg/syringe) and dispersed cells from eight prolactinomas, four GH-secreting and two nonsecreting adenomas (1-3 x 10(6) cells/syringe) were perifused using a Krebs-Ringer culture medium. After 1 h of equilibration the perifusion medium was collected every 2 min (1 mL/fraction) for 3 h. TRH, PRL, and GH were measured by RIA under basal conditions and in the presence of 10(-10) to 10(-6) mol/L dopamine (DA), alone or concomitant with haloperidol, or in the presence of 10(-10) or 10(-6) mol/L somatostatin. Both normal pituitary fragments and pituitary adenomatous cells (from all types of adenomas studied) spontaneously released TRH in vitro. TRH was detected in the perifusion medium either immediately after the end of the equilibration period or 30-60 min later. The molecular identity of TRH was assessed by high pressure liquid chromatography. There was no difference in the profile and the rate of TRH secretion between normal and tumoral tissues, and no correlation was found between the level of TRH release and that of PRL or GH secretion. DA stimulated TRH release from normal pituitaries and from PRL- and GH-secreting adenomas at doses as low as 10(-10) mol/L. A concomitant decrease in PRL and GH release was observed from adenomatous cells and in one case of normal tissue. Haloperidol (10(-7) mol/L) antagonized the effect of 10(-8) mol/L DA on both TRH and PRL secretion in normal pituitary and in prolactinomas. DA had no effect on TRH release from two nonsecreting tumors. The amounts of TRH released during 1 h of perifusion were 60-1640 pg/2 mg wet wt tissue in normal pituitaries and 54-2174 pg/10(6) cells in adenomas; these values were very high compared to those precedently reported within the tissues. These results indicate that pituitary cells can release TRH in vitro and suggest that TRH might be synthesized in situ. We suggest that TRH could act on pituitary hormone secretion and/or cell proliferation via a paracrine and/or an autocrine mechanism.
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PMID:Normal and adenomatous human pituitaries secrete thyrotropin-releasing hormone in vitro: modulation by dopamine, haloperidol, and somatostatin. 197 64

The effects of short and long-term haloperidol treatment on somatostatin concentration and specific binding in rat cerebral cortex and hippocampus were examined using the binding ligand 125I-Tyr1-somatostatin. Haloperidol treatment did not affect the concentration of somatostatin-like immunoreactivity in the two brain areas. Nevertheless, long-term, and not short-term, haloperidol treatment decreased the number of somatostatin receptors in the cerebral cortex and hippocampus. No significant differences in the apparent binding affinity values were seen after haloperidol treatment. When added at the time of the binding assay haloperidol 34.2 microM produced a 42% and 27% decrease in cerebrocortical and hippocampal membrane somatostatin receptors respectively.
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PMID:Long-term haloperidol treatment decreases somatostatin binding in rat brain. 256 56

Intracerebroventricular (i.c.v.) administration of somatostatin or SMS 201-995 induces excessive grooming behavior in rats. The grooming inducing effect of somatostatin is rather weak, as doses of 300 ng or less did not result in increased total grooming scores. In contrast a dose of 10 ng SMS 201-995 already significantly increased the total grooming scores. However, doses of 100 ng and more did not further increase the total grooming scores reached with a 50 ng dose of this peptide. Systemic administration of SMS 201-995 in doses up to 900 micrograms did not result in excessive grooming behavior. The patterns of excessive grooming induced by i.c.v. SMS 201-995 and somatostatin were characterized by a predominant display of scratching. Since peptide-induced scratching is mainly due to activation of opiate receptor systems it is suggested that opiate receptors are involved in the behavioral response to SMS 201-995 and somatostatin administration. This suggestion is further supported by the suppressive effect of naloxone on excessive grooming induced by these peptides. Haloperidol and neurotensin also suppress the excessive grooming induced by somatostatin but not that induced by SMS 201-995. Finally, tolerance developed to the grooming-inducing effect of SMS 201-995 and somatostatin. In addition there was cross tolerance between somatostatin and SMS 201-995.
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PMID:Excessive grooming induced by somatostatin or its analog SMS 201-995. 289 14

Endogenous opioid peptides appear to play a role in the initiation of feeding. Butorphanol, an exogenous opiate which preferentially generalizes to the kappa-sigma opiate receptors, is a potent initiator of feeding. In these studies, we examined the effect of peripherally administered putative satiety substances, cholecystokininoctapeptide, somatostatin, bombesin, gastrin-releasing peptide, thyrotropin-releasing hormone, calcitonin and glucagon on butorphanol induced feeding. With the exception of bombesin, all the other putative satiety factors required 2 to 32 times as high a dose to significantly suppress feeding following butorphanol compared to the dosages required to suppress starvation or tail pinch induced feeding. Bombesin appeared to be approximately equipotent in all systems tested. Haloperidol and atropine both suppressed butorphanol induced feeding supporting our previous hypothesis of an integral relationship between acetylcholinergic-dopaminergic and opioid mechanisms in the initiation of feeding. The findings reported here are compatible with an important role for opioid mechanisms in the initiation of feeding.
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PMID:The effect of peripherally administered satiety substances on feeding induced by butorphanol tartrate. 631 70

The concentrations of neuropeptide Y (NPY) and somatostatin (SS) have been said to be altered in the brain and cerebrospinal fluid of schizophrenic patients. This alteration could result from the neuroleptic treatment. Therefore, it is of interest to evaluate effects of long-term treatment with neuroleptics on the peptide concentrations in the brain. Haloperidol (HPD) is one of the most frequently used neuroleptics for the treatment of schizophrenia. We determined regional brain levels of NPY and SS following HPD administration in the rat. A single intraperitoneal injection of HPD, at a dose of 1 mg/kg, did not affect peptide levels in the brain regions studied. Four weeks after an intramuscular deposit injection of HPD decanoate, 50 mg/kg, NPY concentrations were increased in a number of areas of the cerebral cortex. SS content was also significantly increased in the lateral prefrontal cortex and anterior cingulate cortex. Both peptide levels were decreased in the striatum. These results suggest that the reduction found in these peptides' levels in the cerebral cortex of the brain from schizophrenic patients may not be the consequence of HPD treatment and that these peptides' levels might be increased in the cerebral cortex of the brain of schizophrenic patients following the treatment with HPD.
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PMID:Increases in cortical neuropeptide Y and somatostatin concentrations following haloperidol-depot treatment in rats. 853 77

Behavioral and biochemical responses to D1 and D2 dopamine (DA) agonists were used to evaluate the participation of striatal peptidergic mechanisms in the motor function alterations that attend chronic neuroleptic treatment. Rats, given haloperidol (1 mg/kg, i.c.) for 21 consecutive days, were randomly allocated to one of the following treatments: the D1 agonist SKF 38393, the D2 agonist quinpirole, their combination or saline. Stereotyped behavior and neuropeptide levels were evaluated after 5 days treatment and 4 days washout. Haloperidol increased most oral behaviors including licking, chewing and biting as well as striatal enkephalin and somatostatin levels. Subsequent treatment with SKF 38393 diminished the haloperidol-induced increase in licking and chewing; quinpirole reduced chewing behavior. The administration of both agonists together decreased chewing and biting. Neither DA agonist alone, nor their combination, reduced the haloperidol-induced increase in enkephalin levels. Both SKF 38393 and quinpirole, when given alone, tended to decrease the haloperidol-induced increase in somatostatin levels; when both D1 and D2 agonists were administered together, somatostatin levels declined significantly. These results suggest that somatostatin- but not enkephalin-containing striatal neurons contribute to the expression of haloperidol-induced stereotypies.
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PMID:Effect of long-term haloperidol treatment on striatal neuropeptides: relation to stereotyped behavior. 888 54

Antipsychotics are established drugs in schizophrenia treatment which, however, are not free of side effects. Lipid rafts are critical for normal brain function. Several G protein-coupled receptors, such as somatostatin (SRIF) receptors, have been shown to localize to lipid rafts. The aim of this study was to investigate whether haloperidol treatment affects the composition and functionality of lipid rafts in SH-SY5Y neuroblastoma cells. Haloperidol inhibited cholesterol biosynthesis, leading to a marked reduction in cell cholesterol content and to an accumulation of sterol intermediates, particularly cholesta-8,14-dien-3beta-ol. These changes were accompanied by a loss of flotillin-1 and Fyn from the lipid rafts. We next studied the functionality of the SRIF receptor. Treatment with haloperidol reduced the inhibitory effect of SRIF on adenylyl cyclase (AC) activity. On the other side, haloperidol decreased basal AC activity but increased forskolin-stimulated AC activity. Addition of free cholesterol to the culture medium abrogated the effects of haloperidol on lipid raft composition and SRIF signaling whereas the AC response to forskolin remained elevated. The results show that haloperidol, by affecting cholesterol homeostasis, ultimately alters SRIF signaling and AC activity, which might have physiological consequences.
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PMID:Effects of the antipsychotic drug haloperidol on the somastostatinergic system in SH-SY5Y neuroblastoma cells. 1945 89