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 effects of somatostatin, administered into different areas of the brain were studied in preliminary picrotoxin-kindled rats. The injection of somatostatin into the lateral ventrical of the brain (i.c.v.) (1.8 nmol), the hippocampus (0.6 nmol) or the amygdala (0.6 nmol), resulted in a decrease in the severity of the picrotoxin-induced convulsions. Application of the peptide into the caudate-putamen or the substantia nigra reticulata did not alter the behavioural manifestations of the kindled seizures. The local injection of anti-somatostatin serum (1:5) into the hippocampus increased the severity of the kindled convulsions and blocked the anticonvulsive effect of somatostatin, given intraventricularly. Local administration of anti-somatostatin serum into the amygdala did not alter the kindled seizures and did not abolish the anticonvulsive action of somatostatin given intraventricularly. It is concluded that somatostatin could take part in endogenous control of seizures through a suppressant influence on limbic structures; the hippocampus could be a specific site for the antiepileptic action of somatostatin.
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PMID:Effects of somatostatin and anti-somatostatin serum on picrotoxin-kindled seizures. 135 54

We tested the hypothesis that brain somatostatin levels modify two motor behaviors evoked by ICV infusions of nicotine. Unrestrained, awake rats were given fixed-concentration infusions of nicotine until the prostration/immobility (PI) syndrome and convulsions were produced. Infusion duration ranged from 0.9 to 1.2 min for the PI syndrome and 2.5 to 4.9 min for the convulsions. Octreotide, a stable somatostatin analog (4.5 micrograms, ICV), significantly raised the threshold for nicotine convulsions 1.0 and 5.5 h after pretreatment but not at 24 or 48 h. Cysteamine, a somatostatin releaser and depletor (0.35-0.75 mg/rat, ICV), also caused a dose-dependent increase in seizure threshold. Similarities in the response to octreotide and cysteamine suggest that depression of nicotine convulsions by cysteamine may be mediated by release of endogenous somatostatin. Neither octreotide nor cysteamine altered the threshold for the PI syndrome. These results support the view that one motor behavior evoked by nicotine is subject to control by somatostatin whereas another is not.
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PMID:Differential effects of octreotide on motor responses to nicotine in rats. 147

To study the possible involvements of neuropeptides in the occurrence of convulsion, pentylenetetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neurotensin (NT), and the maximal number of binding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measured. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) on the convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Membrane fractions were incubated with increasing concentrations of 125I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the specific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion appeared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 +/- 4.4 sec. One hour after the administration, neurotensin-like immunoreactivity (NTLI) concentration was reduced from 4.7 +/- 0.6 to 2.3 +/- 0.1 ng/g wet wt (p less than 0.01) and the Bmax of NT receptor from 17.2 +/- 2.8 to 10.8 +/- 1.1 fmol/mg protein (p less than 0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pretreatment with intracerebroventricular (icv) administration of 30 micrograms/10 microliters NT 30 min before the 50 mg/kg PTZ administration shortened the duration of the convulsion from 135.0 +/- 42.8 to 11.5 +/- 11.9 sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Involvements of neuropeptides in pentylenetetrazol-induced convulsion in rats and effects of TRH and ceruletide on the convulsion]. 197 Sep 33

Intrathecal (i.t.) injection of somatostatin has been reported to depress nociceptive reflexes as well as to cause severe disturbance of somatomotor performance. The present study was designed to assess the dependence of these effects on the dose and the interval between implantation of the catheter and i.t. injection of somatostatin in rats. The effects produced by i.t. injection of somatostatin consisted of an increase in the response latencies of nociceptive responses to noxious heat, impairment of motor performance and grooming behavior, convulsions, and death. Except for grooming behavior, these were related in incidence and degree to the dose and the interval, the potency of somatostatin being highest at short intervals. Sham operations also affected the effectiveness of somatostatin.
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PMID:Intrathecal somatostatin produces effects dependent on the interval between catheter implantation and drug injection. 197 15

In order to investigate the potential antagonistic actions of the two main neuroregulators of the somatotropinergic system (GRF-SS-GH-SM axis), growth hormone-releasing factor (GRF) and somatostatin (SS) at the central level, the effects of GRF and SS on locomotor activity (LA) were studied in a computerized system. Male Wistar rats (N = 6-9 per group) received i.p. or i.c.v. GRF(1-44)NH2 or SS(1-14) in doses ranging from 0.1-30 micrograms, and LA was automatically recorded in the OUCEM-86 system (Osaka University Computerized Electronic Maze) for 30-min periods. The peripheral administration of SS (1 microgram, i.p.) did not alter LA, while GRF (1 microgram, i.p.) increased LA from 20.35 +/- 4.18 to 36.25 +/- 6.98 IO/min (p less than 0.005). After central injection, SS (1 microgram; i.c.v.) decreased LA from 31.16 +/- 6.90 to 20.88 +/- 2.82 IO/min (p less than 0.005) and GRF (1 microgram, i.c.v.) increased LA to 47.60 +/- 5.35 IO/min (p less than 0.005). SS- and GRF-induced LA changes were time- and dose-dependent (SS: ED50 = 1.83 nmol, Emax = 6.10 nmol; GRF: ED50 = 99.1 pmol, Emax = 1.98 nmol). The maximum effect of GRF appeared during the first 5 min, showing activity 10-15 sec post-injection, while the lowest activity induced by SS was registered 15-30 min after injection, although a significant reduction in LA was detected 5-10 sec after i.c.v. administration. With doses higher than 10 micrograms (i.c.v.) SS provoked "barrel rotation", tremors and stereotyped behaviors. The GRF-induced hyperkinetic syndrome showed a linear pattern with doses up to 10 micrograms, and a plateau with 10-15 micrograms. Doses higher than 20 micrograms induced convulsion, uncontrolled movements and a high death rate during the following 12-24 h. In conclusion, according to the present results, GRF and SS exert antagonistic effects on LA in a time- and dose-dependent manner, the former stimulating LA, and the latter inhibiting it.
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PMID:Antagonistic effects of growth hormone-releasing factor (GRF) and somatostatin on locomotor activity: GRF-induced hyperkinetic syndrome. 198 32

Recent studies have shown that erythromycin lactobionate (EMLB) acts as a motilin agonist and is able to accelerate gastric emptying in diabetic gastroparesis. Using the rabbit as a model, we have studied the changes in motilin receptor density induced by EMLB (a motilin agonist) and octreotide (a somatostatin analogue and an inhibitor of motilin secretion). Binding studies were performed with antral smooth muscle tissue homogenates using iodinated nor-leucine13-porcine-motilin, and binding parameters were obtained from computerized fits to displacement curves. The contractile capacity towards motilin (10(-7) M) and EMLB (10(-5) M) was measured isotonically on duodenal segments and the response was expressed relative to the maximum obtained with ACh (10(-4) M). The first hours after the last i.v. administrations of EMLB (50 mg/day given on 3 consecutive days), motilin binding was completely abolished to 0.02 +/- 0.006 fmol/mg protein, compared to the control group (0.64 +/- 0.12 fmol/mg protein). The effect was dose-related: total doses of 17.5 mg, 87.5 mg, 175 mg EMLB reduced motilin binding and contractility towards motilin and EMLB to respectively 95 +/- 10, 82 +/- 5%; 36 +/- 9, 38 +/- 9%; 3 +/- 1, 24 +/- 2% of the control values. The effect was also long lasting: binding was still reduced to 60% of the control value 48 h after the highest dose. In contrast, octreotide induced a marked but short lasting upregulation. After 3 daily s.c. injections of 5 micrograms, Bmax rose to 13.6 +/- 1.9 fmol/mg protein (P less than 0.05). It was already obtained 1 h after 3 x 2.5 micrograms/24 h. The changes in receptor-density were not related to changes in affinity. We conclude that motilin receptors can be regulated by EMLB and octreotide presumably because one compound mimicks hypermotilinemia, the other one induces hypomotilinemia.
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PMID:Effect of erythromycin and of octreotide on motilin receptor density in the rabbit. 203 24

Growth hormone releasing factor (GRF) neurons in the arcuate nucleus of the hypothalamus and somatostatin (SRIF) neurons in the anterior periventricular region of the hypothalamus act to control the release of growth hormone from the anterior pituitary. To investigate the possibility that the growth-controlling functions of these cells might be compromised by injuries to the developing brain, it is important to know the details of the production and differentiation of these small, specialized cell groups. The overall pattern of cell production in the hypothalamus is known from autoradiographic studies with general nuclear stains, but no data are available on the birthdates (times of final mitoses) of GRF-producing cells. The present study was undertaken to determine when the GRF cells form. Counts of immunocytochemically identified GRF cells labeled on given days were taken from serial coronal sections through the hypothalamus of adult rats labeled on the 10th-17th days of gestation (day of finding a vaginal plug = day 1). As has been shown for the hypothalamus in general, the GRF cells showed a gradient of production from anterior to posterior. The peak of anterior cell proliferation was on day 13, middle cells on day 14, and posterior cells on day 15. These dates are 1 or 2 days earlier than those of GRF-negative cells in the same regions. No lateral to medial gradient of formation was seen in GRF cells. Rather, the laterally placed cells along the base of the brain and those surrounding the ventromedial nucleus formed simultaneously with the GRF cells of the arcuate nucleus. The birthdating results presented here are in agreement with the results of studies of teratogens which suggest that rat postnatal growth is reduced most severely by exposure to neurotoxic agents on days 12 or 13 of gestation. On the basis of data for the whole hypothalamus, such treatments would appear to be too early to interfere with cell production for the arcuate nucleus, but the timing fits the period of vulnerability as defined by the birthdates determined in the present study for the subpopulation of cells destined to produce GRF.
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PMID:Birthdates of the growth hormone releasing factor cells of the rat hypothalamus: an autoradiographic study of immunocytochemically identified neurons. 210 44

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.
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PMID:Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin. 242 20

Recently, several systems of neuropeptides have been demonstrated to have anticonvulsant action in some forms of epilepsy to some extent. However, considerably less knowledge has been taken to their involvement in convulsive disorders either with regard to the development, expression or control of seizures. In this study, therefore, we examined the influence of amygdaloid kindling, an experimental model of temporal lobe epilepsy, on thyrotropin-releasing hormone (TRH), somatostatin (SS), cholecystokinin (CCK) and substance P (SP) content in the amygdala/piriform cortex and hippocampus. Male Sprague-Dawley rats were implanted bipolar electrodes into the left amygdala under pentobarbital anesthesia. Daily kindling stimulation was made to the left amygdala with 1 sec, 60 Hz, 400 microA, until 5 consecutive fully kindled generalized convulsive seizures were elicited. Subsequently, amygdaloid kindled rats were decapitated 30 min, 24 hrs, 48 hrs, 7 days and 21 days after the last amygdaloid stimulation, and the amygdala/piriform cortex and hippocampus were dissected. Control animals only received chronic electrodes, but no stimulation was delivered. The immunoreactivity of TRH, SS, CCK and SP was examined by methods of specific radioimmunoassay. The TRH content in these two brain regions significantly increased 24 hrs after the last kindled convulsion. This increase became maximal 48 hrs after the last convulsion: about 3-fold and 4-fold of the control in the amygdala/piriform cortex and hippocampus, respectively. Such increases in the TRH content tended to persist for 7 days, but returned to the control level 21 days after the last convulsion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of amygdaloid kindling on thyrotropin-releasing hormone, somatostatin, cholecystokinin and substance P contents of the amygdala/piriform cortex and hippocampus of rats]. 246 12

Wistar rats were injected with a convulsant doze of pentylenetetrazol (PTZ) (50 mg/kg, i.p.). Somatostatin-like immunoreactivity (SLI) and 125I-Tyr11-somatostatin binding were measured in various brain areas immediately after PTZ injection, after the first head twitches, and 15 minutes, 1 h, 4 h, and 24 h after generalized tonic-clonic convulsions. SLI tended to decrease in the striatum (p less than 0.02), frontal cortex, hippocampus, and hypothalamus 1 hour after convulsion. Specific somatostatin binding remained stable. According to our results, somatostatin is not connected to initiation or spread of seizure but may play some role in depressing seizures.
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PMID:Somatostatin-like immunoreactivity and somatostatin receptor binding in rat brain before and after pentylenetetrazol-induced convulsion. 286 41


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