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)

Previous studies from this and other laboratories demonstrated that many embryonic sensory ganglion cells in the rat transiently express the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most mature sensory neurons. We, therefore, sought to determine whether transient expression was uniquely associated with catecholaminergic traits, or, alternatively, whether embryonic ganglion cells transiently expressed peptidergic properties as well. Of the four peptides examined (somatostatin [somatotropin release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene-related peptide (CGRP), and substance P (SP)), only SRIF was found to be transiently expressed during early stages of sensory gangliogenesis. Surprisingly, SRIF immunoreactivity was observed in virtually all cranial and spinal sensory ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling, intense SRIF immunoreactivity was also observed in the central and peripheral processes of E12.5 sensory neurons, suggesting the peptide may be released from nerve endings. The time course of SRIF appearance in cranial ganglion cells paralleled that previously described for TH, and double-labeling studies revealed extensive co-localization of these two phenotypes. By E16.5, however, the number of neurons expressing SRIF had diminished markedly, indicating that SRIF is only transiently expressed by most sensory neurons during early stages of ganglion development. An unexpected finding was that transient expression of SRIF is also a prominent feature of sympathetic ganglion cells; however, the temporal pattern of staining in the sympathetic and sensory ganglia differed substantially. Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled. This contrasted sharply with the adult SCG, in which only low levels of SRIF expression were found. These findings demonstrate that SRIF peptide is transiently expressed at high levels in peripheral sensory and sympathetic neurons during embryogenesis. The time course and widespread distribution of SRIF expression indicates that the peptide may play a role in early stages of ganglion cell growth and development. Moreover, these data, in conjunction with previous studies demonstrating SRIF immunoreactivity in developing central neurons, suggest that transient expression of this peptide is a common property of diverse neuronal cell types.
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PMID:Transient expression of somatostatin peptide is a widespread feature of developing sensory and sympathetic neurons in the embryonic rat. 135 5

The general morphology of the intramural innervation of the myenteric plexus of the axolotl stomach has been investigated using antisera raised against neuron-specific enolase and a microtubule-associated protein. Additionally, the occurrence of serotonin and several peptidergic neurotransmitter/neuromodulator substances was studied. Immunoreactivity for galanin, vasoactive intestinal polypeptide, substance P and neuromedin U was found in both fibres and intrinsic perikarya, whereas the serotonin and calcitonin gene-related peptide-like-substance-containing nerve fibres seemed to be of extrinsic origin. The axolotl stomach myenteric plexus appeared to be devoid of enkephalin-, neuropeptide Y-, somatostatin- and bombesin-like immunoreactive nerve fibres and nerve cell bodies. Double labelling experiments revealed the presence of a subpopulation of substance P/calcitonin gene-related peptide-like immunoreactive nerve fibres. Contrary to mammals, no coexistence of neuromedin U and substance P was found. Our findings illustrate that besides a number of similarities, considerable species differences exist between urodeles and anurans with regard to the organization of the enteric nervous system.
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PMID:Morphological features of the myenteric plexus of the stomach of the axolotl, Ambystoma mexicanum, revealed by immunocytochemistry. 137 7

Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effect of galanin, a neuropeptide that stimulates GH secretion, on GH-releasing hormone (GHRH)-induced GH secretion in adult patients with nonendocrine diseases who were under daily immunosuppressive glucocorticoid therapy. Six normal subjects (four men, two women) and seven steroid-treated subjects (three men, four women) were studied. GHRH-induced GH secretion was evaluated during a 40-minute intravenous (i.v.) infusion of saline or porcine galanin (12.5 micrograms/min). During saline infusion, steroid-treated patients showed a blunted GH response to GHRH (GH peak, 8.1 +/- 2.8 micrograms/L), as compared with normal subjects (GH peak, 23.8 +/- 3.9 micrograms/L). During galanin infusion, the GH response to GHRH was significantly enhanced (GH peak, 46.6 +/- 9.4 micrograms/L, P less than .05), as compared with saline infusion in normal subjects. In contrast, galanin infusion did not enhance the GH response to GHRH (GH peak, 16.6 +/- 6.5 micrograms/L), as compared with saline infusion in steroid-treated patients. The area under the GH-response curves was also significantly (P less than .05) lower in steroid-treated subjects, as compared with normal subjects. Thus, galanin failed to normalize or enhance the GH response to GHRH in patients treated long-term with glucocorticoids. It can be hypothesized that galanin does not elicit GH secretion by decreasing hypothalamic somatostatin tone.
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PMID:Effect of galanin on growth hormone-releasing hormone-stimulated growth hormone secretion in adult patients with nonendocrine diseases on long-term daily glucocorticoid treatment. 137 12

The rostral ventrolateral medulla (RVLM) contains sympathoexcitatory neurons that exert a powerful control over the sympathetic outflow to the cardiovascular system. In the cat there is a concentration of such neurons (but not neurons subserving other functions) within a narrow longitudinal column in the RVLM termed the subretrofacial (SRF) nucleus. Furthermore, it has been suggested that there are subgroups of cells, located at different rostrocaudal levels of the SRF nucleus, that preferentially or exclusively control different vascular beds (e.g. in the kidney and hindlimb). The aim of this study was to map quantitatively the rostrocaudal distribution within the nucleus of different cell types, defined according to morphological and/or chemical criteria, and to correlate this with the regional vasomotor effects (in hindlimb and kidney) evoked by stimulation of SRF cells at the corresponding rostrocaudal levels. SRF cells were highly heterogeneous with respect to both their morphology and chemical properties. They varied greatly in size (equivalent diameter ranging from 10-40 microns) as well as in shape and orientation. An immunohistochemical examination using the avidin-biotin procedure revealed that many SRF cells (estimated 57% of all SRF cells) were immunoreactive for tyrosine hydroxylase (TH, a marker of catecholamine cells). In addition, there were SRF cells immunoreactive for neuropeptide Y (NPY, 11% of total), enkephalin (ENK, 16% of total), and serotonin (5HT, 10% of total), but not for substance P, galanin or somatostatin. Different cell types, defined according to their morphology and/or chemical properties, were unevenly distributed throughout the nucleus. In the most caudal part of the SRF nucleus, virtually all cells were TH-positive, and the large majority (estimated 80%) were NPY-positive, suggesting that many cells at this level contained both TH and NPY. In contrast, in the most rostral part of the SRF nucleus, only 30% of cells were TH-positive, and no NPY-positive cells were observed. Both 5HT- and ENK-positive cells were found throughout the rostrocaudal extent of the nucleus, but predominantly within its rostral part. Furthermore, TH-positive cells in the rostral SRF nucleus were on average significantly larger (mean equivalent diameter 18-43% greater) than TH/NPY-positive cells in the caudal part of the nucleus, but smaller than 5HT- or ENK-positive cells at the same level. Overall, rostral cells (regardless of their chemical type) were larger than caudal cells within the SRF nucleus (mean equivalent diameter 13-28% greater).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rostrocaudal differences in morphology and neurotransmitter content of cells in the subretrofacial vasomotor nucleus. 137 28

To determine whether norepinephrine (NE) and galanin are coreleased during reflex activation of the sympathetic nervous system by hypoglycemia, we administered insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma. Insulin injection produced hypoglycemia [plasma glucose (PG) = 34 +/- 3 mg/dl] but did not activate pancreatic noradrenergic (delta pancreatic NE output = +20 +/- 130 pg/min) or galaninergic nerves (delta GLIR output = +40 +/- 50 fmol/min). To determine whether more severe hypoglycemia would activate these nerves, insulin was administered to dogs infused with somatostatin (SS; 2.5 micrograms/min) to block the counterregulatory increase of glucagon secretion. SS reduced the glucagon response to hypoglycemia by greater than 90%, which allowed PG to decrease to 14 +/- 1 mg/dl. Pancreatic NE output increased by 470 +/- 140 pg/min (P less than 0.005); however, pancreatic GLIR output did not increase significantly (delta = +70 +/- 50 fmol/min). When SS was discontinued, pancreatic NE output increased by 490 +/- 200 pg/min (P less than 0.025), and GLIR output increased by an additional +160 +/- 70 fmol/min (P less than 0.025; total delta from baseline = +230 +/- 90 fmol/min, P less than 0.025), suggesting that SS may restrain pancreatic NE and galanin release. Pancreatic NE and GLIR spillover were also increased during severe hypoglycemia when ganglionic neurotransmission was partially impaired with hexamethonium but not when the neural pathway was interrupted by spinal cord transection. We conclude that NE and galanin are coreleased from pancreatic sympathetic nerves when these nerves are centrally activated during severe hypoglycemia in halothane-anesthetized dogs.
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PMID:Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs. 137

Neuropeptide Y (NPY) is a powerful appetite stimulant, and hypothalamic concentrations rise after food deprivation and in experimental diabetes. Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin in chow-fed rats and in rats with dietary obesity, and examined the effect of dexfenfluramine on these peptides in this model. Sixty-five rats were fed a palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs. 113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or 28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay. Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was significantly higher in the palatable diet group compared to chow-fed controls (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than 0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at reducing weight gain in the animals fed the palatable diet, this did not result in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be of importance in diet-induced obesity but the weight loss produced by dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.
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PMID:Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats. 138 31

The hypothalamo-neurohypophyseal tract is known to contain the classical neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin, methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), and galanin are co-stored with vasopressin and/or oxytocin. Recent immunohistochemical studies have revealed the existence of a low to moderate number of substance P-, vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were distributed throughout the organ, whereas somatostatin-immunoreactive fibers were present in the proximal part of the organ. The positive nerve endings were either large in size resembling classical nerve terminals related to perivascular spaces, or smaller similar to peptidergic fibers as described in the CNS. These results indicate that these neuropeptides may be either co-stored with the classical neurohypophyseal hormones or contained in another system of afferents to the organ. The probably distinct functional roles of these neuropeptides in the physiology of the neurohypophysis are discussed.
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PMID:Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo-neurohypophyseal tract: experimental immunohistochemical studies. 138 83

Single- and dual-labelling immunohistochemistry were used to determine the distribution and coexistence of neuropeptides in perivascular nerves of the large arteries and veins of the snake, Elaphe obsoleta, using antibodies for vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, neuropeptide Y, galanin, somatostatin, and leu-enkephalin. Blood vessels were sampled from four regions along the body of the snake: region 1, arteries and veins anterior to the heart; region 2, central vasculature 5 cm anterior and 10 cm posterior to the heart; region 3, arteries and veins in a 30-cm region posterior to the liver; and region 4, dorsal aorta and renal arteries, renal and intestinal veins, 5-30 cm cephalad of the vent. A moderate to dense distribution of vasoactive intestinal polypeptide-like immunoreactive fibres was found in most arteries and veins of regions 1-3, but fibres were absent from the vessels of region 4. The majority of vasoactive intestinal polypeptide-like immunoreactive fibres contained colocalized substance P-like immunoreactivity, and these fibres were unaffected by either capsaicin or 6-hydroxydopamine (6-OHDA) pretreatment. In the anterior section of the snake, the vagal trunks contained many cell bodies with colocalized vasoactive intestinal polypeptide and substance P-like immunoreactivity. It is suggested that the vasoactive intestinal polypeptide/substance P-like immunoreactive cell bodies and fibres are parasympathetic postganglionic nerves. Neuropeptide Y-like immunoreactive fibres were observed in all arteries and veins, being most dense in regions 3 and 4. The majority of these fibres also contained colocalized galanin-like immunoreactivity, and were absent in tissues from 6-OHDA pretreated snakes, suggesting that neuropeptide Y and galanin are colocalized in adrenergic nerves. A small number of neuropeptide Y-like immunoreactive fibres contained vasoactive intestinal polypeptide but not galanin, and were unaffected by 6-OHDA treatment. All calcitonin gene-related peptide-like immunoreactive fibres contained colocalized substance P-like immunoreactivity, and these fibres were observed in all vessels, being particularly dense in the carotid artery and jugular veins. All calcitonin gene-related peptide/substance P-like immunoreactive fibres appeared damaged after capsaicin treatment suggesting they represent fibres from afferent sensory neurons. A sparse plexus of somatostatin-like immunoreactive fibres was observed in the vessels only from region 4. No enkephalin-like immunoreactive fibres were found in any blood vessels from any region. This study provides morphological evidence to suggest that there is considerable functional specialization within the components of the rat snake peripheral autonomic system controlling the circulation, in particular the regulation of venous capacitance.
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PMID:The distribution and colocalization of neuropeptides in perivascular nerves innervating the large arteries and veins of the snake, Elaphe obsoleta. 138 80

The present work was undertaken to determine by immunocytochemical methods which of the putative enteric neurotransmitters are contained in axons supplying the guinea-pig taenia coli and what proportion of axons is accounted for by the presence of these substances. Numerous fibres displayed immunoreactivity for dynorphin (DYN), enkephalin (ENK), gamma-aminobutyric acid (GABA), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in contrast to other gut regions, fibres showing immunoreactivity for gastrin-releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5-hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like immunoreactivity (TH-LI) was present in numerous fibres that disappeared after extrinsic denervation, a procedure that did not detectably affect any of the other major groups of fibres. Simultaneous staining of extrinsically denervated preparations revealed that SP-LI and VIP-LI were located in separate fibres, and ultrastructural studies showed these to be 58% and 33% of intrinsic fibres supplying the muscle. Immunoreactivity for the general marker, neuron-specific enolase, was located in 95-98% of axons. ENK-LI and DYN-LI were in the same axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about 85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI fibres, were reactive for NOS. The results imply that the taenia of the guinea-pig caecum is innervated by two major groups of enteric neurons: (i) excitatory neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases, the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained in a smaller population of intrinsic axons. Even though the taenia represents one of the simplest tissues for examining transmission from enteric neurons to intestinal muscle, it shares some of the complexity of other regions, in that four major axon types supply the muscle and both the enteric excitatory and enteric inhibitory neurons contain multiple transmitters.
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PMID:Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum. 138 81

In addition to inducing pituitary tumors in rats, estrogen (E2) markedly increases galanin and PRL gene expression. We previously showed that galanin secretion from pituitary cells in vitro is inhibited by dopamine and somatostatin and stimulated by TRH. The objectives of these in vivo studies were to assess whether the long-acting somatostatin analog SMS 201-995 alters 1) immunoreactive galanin or PRL levels in the anterior pituitary, neurointermediate lobe, hypothalamus, or plasma, 2) pituitary galanin and PRL mRNA levels, and 3) the development of E2-induced pituitary tumors. Ovariectomized Fischer 344 rats were implanted with E2-filled or empty Silastic capsules and treated with or without SMS 201-995 (1.5 mg) via Alzet miniosmotic pumps. Two or 6 weeks later, immunoreactive galanin and PRL levels were determined by RIA. In ovariectomized rats, the somatostatin analog lowered the anterior pituitary content of galanin by 50%, but had no effect on PRL concentrations. E2 increased galanin and PRL levels in the anterior pituitary by 220- and 4-fold, respectively. Concomitant E2 and SMS 201-995 treatment further increased galanin and PRL in the anterior pituitary by 60-80%, but decreased plasma galanin and PRL levels. Likewise, the administration of SMS 201-995 for 2 and 6 weeks inhibited the E2-induced growth of the anterior pituitary. Galanin and PRL mRNA levels were quantified by solution hybridization. Galanin mRNA levels were reduced to undetectable levels in ovariectomized rats treated with SMS 201-995. Furthermore, a 10-fold increase in galanin mRNA levels seen in the presence of E2 was inhibited 80% by SMS 201-995. PRL mRNA levels in E2-treated rats were unchanged by SMS 201-995. We conclude that SMS 201-995 1) lowers plasma galanin and PRL levels in E2-treated rats, 2) elevates the anterior pituitary contents of galanin and PRL in E2-exposed rats, probably through decreased secretion of the hormones, and 3) reduces galanin mRNA levels in E2-treated and untreated ovariectomized rats. Overall, these results establish the differential regulation of galanin and PRL gene expression in vivo by SMS 201-995. Moreover, the data demonstrate that somatostatin receptor agonists may have therapeutic potential for some prolactinomas.
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PMID:Regulation of galanin gene expression in the rat anterior pituitary gland by the somatostatin analog SMS 201-995. 138 97


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