Infusion Of Galanin Research Articles

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

Neurochemical, molecular, immunohistochemical and behavioral methods were used to examine the in vivo effects of the neuropeptide galanin on central 5-HT neurotransmission and on 5-HT1A receptor-mediated responses. Intraventricularly infused galanin caused a long-lasting and dose-dependent reduction of basal extracellular 5-HT levels in the ventral hippocampus of awake rats as measured by microdialysis. Infusion of galanin into the dorsal raphe nucleus (DRN), but not intra-hippocampally, reduced 5-HT release. The effect of i.c.v. galanin on 5-HT release was blocked by the galanin receptor antagonist M35, acting most likely via galanin receptors at the level of the DRN. Galanin also reduced the levels of tryptophanhydroxylase mRNA in the DRN. Therefore, the effects of galanin on 5-HT1A receptor-mediated responses were further investigated. Surprisingly, galanin significantly attenuated the reduction of hippocampal 5-HT release induced by systemic injection of the 5-HT1A receptor agonist 8-OH-DPAT. Galanin also attenuated 8-OH-DPAT-induced hypothermia and locomotor activity in rats. These results indicate that galanin has important inhibitory actions on central 5-HT neurotransmission and on 5-HT1A receptor-mediated events.

Galanin and spatial learning in the rat. Evidence for a differential role for galanin in subregions of the hippocampal formation

Anatomical, neurochemical and behavioural evidence support a role for galanin in hippocampally mediated functions such as spatial learning and memory. To obtain more precise information on this role, galanin (3 nmol/rat) was infused via bilateral chronic cannulae into different areas of the hippocampal formation which are characterized by different galanin receptor subtypes and also by different galanin innervation patterns. The effects of infused galanin on spatial learning were examined in the Morris swim maze. Infusions of galanin into both the dorsal and ventral dentate gyrus, which mainly contain GAL-R2 receptor mRNA and a high degree of galanin–noradrenaline coexistence, significantly retarded spatial acquisition without affecting swim speed or performance in the visible platform test. This spatial learning deficit was fully blocked by pretreatment with the non-selective galanin antagonist M35. Analysis of retention performance suggested that the major effect of intrahippocampal galanin is mediated via a specific disruption of acquisition mechanisms of importance for performance in the probe trial. Galanin infused into the ventral CA1 (a mainly GAL-R1 receptor mRNA expressing region) or into anterior, ventral CA3 regions did not produce any deficits in spatial learning compared to control animals. These results suggest that galanin mediates its action on spatial learning mainly through the GAL-R2 receptor subtype in areas where most of the galanin is present in noradrenergic terminals. A possible role for the GAL-R1 receptor subtype in cognition in the dorsal and ventral hippocampus remains to be defined. The results suggest a differential functional role for galanin and galanin receptor subtypes within subregions of the hippocampal formation.

Differential action of hepatic sympathetic neuropeptides: metabolic action of galanin, vascular action of NPY.

Activation of hepatic nerves increases both hepatic glucose production (HGP) and hepatic arterial vasoconstriction, the latter best described by a decrease of hepatic arterial conductance (HAC). Because activation of canine hepatic nerves releases the neuropeptides galanin and neuropeptide Y (NPY) as well as the classical neurotransmitter norepinephrine (NE), we sought to determine the relative role of these neuropeptides vs. norepinephrine in mediating metabolic and vascular responses of the liver. We studied the effects of local exogenous infusions of galanin and NPY on HGP and HAC to predict the metabolic and vascular function of endogenously released neuropeptide. Galanin (n = 8) or NPY (n = 4) was infused with and without NE directly into the common hepatic artery of halothane-anesthetized dogs, and we measured changes in HGP and HAC. A low dose of exogenous galanin infused directly into the hepatic artery potentiated the HGP response to NE yet had little effect on HGP when infused alone. The same dose of galanin infused into a peripheral vein (n = 8) did not potentiate the HGP response to NE, suggesting that the locally infused galanin acted directly on the liver to modulate NE's metabolic action. In contrast, a large dose of exogenous NPY failed to influence HGP when infused either alone or in combination with NE. Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE. Therefore, both hepatic neuropeptides may contribute to the action of sympathetic nerves on liver metabolism and blood flow. It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction.

Antisecretory effects of galanin and its putative antagonists M15, M35 and C7 in the rat stomach

The neuropeptide galanin has been reported to have a wide range of biological actions both in the central nervous system and in the gastrointestinal tract. Recent works led to the discovery of selective galanin receptor antagonists including M15 (galanin 1-12-Pro-substanceP 5-11-amide), M35 (galanin 1-12-Pro-bradykinin 2-9-amide) and C7 (galanin 1-12-Pro-spantide-amide). These antagonists were shown to competitively inhibit actions of galanin in the central nervous system. The present study was designed to investigate the effect of galanin, M15, M35 and C7 on gastric acid secretion and gastric emptying. Pentagastrin-stimulated gastric acid secretion was inhibited by galanin (0.1–9 nmol.kg –1.h –1, i.v.) in a dose-dependent manner (ID 50 = 1.8 ± 0.3 nmol.kg –1.h –1). When 9 nmol.kg –1.h –1 galanin infusion was given, inhibition became almost complete. M15, M35 and C7 (1–9 nmol.kg –1.h –1) did not modify responses of the stomach to galanin, but acted as agonists of galanin on acid secretion. Neither galanin nor its putative antagonists affected the emptying of non-caloric liquids from the stomach. In conclusion, galanin may play an antisecretory role in the regulation of gastric acid secretion but not in the control of gastric emptying of liquids in rats. Its antisecretory action on the stomach is mediated by galanin receptors that are distinct from those in the central nervous system.

Effects of galanin infusion on GH secretion and GHRH-induced GH release in prepubertal male lambs

The coexistence of galanin (GAL) with some classical neurotransmitters suggests that it may exert a role as a neuroendocrine modulator. The aim of this study was to investigate the GH response to porcine galanin (p-GAL) in prepubertal male lambs. In the experiments A and B the i.v. infusion of galanin (5 μg/kg) for 60 min was carried out alone (Experiment A) or combined with an i.m. injection of GHRH (0.5 μg/kg) 30 min after infusion (Experiment B); in the Experiment C, galanin (5 μg/kg) was infused for 300 min. Galanin infusion was not effective in increasing GH baseline levels ( P > 0.08); however galanin potentiated ( P < 0.01) the GH responsiveness to GHRH. The prolonged galanin infusion caused a significant increase in GH plasma levels and pulse frequency. These observations support the hypothesis that galanin may be involved in the regulation of somatotropic axis in young animals by modulating both stimulatory and inhibitory hypothalamic factors.

The canine sympathetic neuropeptide galanin: a neurotransmitter in pancreas, a neuromodulator in liver.

Our laboratory has investigated the role of the neuropeptide galanin in the sympathetic neural control of both the canine endocrine pancreas and liver. Galanin mRNA and peptide were found in the neuronal cell bodies of the celiac ganglion, which projects fibers to both organs. Galanin fibers formed dense networks around the islets. Galanin was released from these nerves and the amount released appeared sufficient to markedly inhibit basal insulin secretion. We therefore propose that galanin is a sympathetic neurotransmitter in canine endocrine pancreas. Galanin was also found in hepatic nerves usually co-localized with tyrosine hydroxylase, a sympathetic marker. Further, intraportal administration of the sympathetic neurotoxin, 6-hydroxydopamine, abolished galanin staining in the hepatic parenchyma. We evaluated the role of galanin in mediating the actions of sympathetic nerves to increase hepatic glucose production and decrease hepatic arterial conductance. Local infusion of synthetic galanin had little effect by itself, but it did potentiate the action of norepinephrine to stimulate hepatic glucose production, demonstrating a neuromodulatory action. In contrast, galanin had no effect on hepatic arterial blood flow. We therefore propose that in the liver galanin functions as a neuromodulator of norepinephrine's metabolic action.

Autoradiographic mapping of cerebral blood flow responses to cholinergic stimulation of the rat substantia innominata: modulatory effect of galanin

In order to analyze the precise cerebrovascular effects of a specific cholinergic stimulation of the rat substantia innominata and their modulation by galanin, cerebral blood flow was measured by the [ 14C]-iodoantipyrine autoradiographic method in anesthetized (urethane and α-chloralose), artificially ventilated male Sprague–Dawley rats that received a microinjection into the substantia innominata of saline ( n=7), or 63 pmol of galanin ( n=8), or 50 nmoles of carbachol ( n=6) or a coinjection of carbachol and galanin ( n=8). Significant carbachol-induced cerebral blood flow increases were noted in ipsilateral cortices (+36%, p<0.01 in the cingulate to +82%, p<0.01 in the parietal somatosensory cortices), but also in ipsilateral hippocampus and ipsilateral thalamus. These cerebral blood flow increases were abolished by the coinjection of carbachol and galanin, while infusions of galanin alone failed to affect cerebral blood flow. Cholinergic stimulation of the substantia innominata represents thus a good model for the analysis of the detailed pharmacological properties of the cholinergic vasodilatatory basalocortical system. The existence of an inhibitory galaninergic modulation of this system could be of particular interest, in terms of cerebrovascular reactivity, in various neurodegenerative states.

Inhibition of gastric acid secretion by galanin in rats: Relation to endogenous histamine release

Inhibitory effect of galanin on basal and secretagogs-stimulated gastric acid secretion was investigated in urethane-anesthetized rats. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and either gastric acid or alkaline secretion was determined by titrating the perfusate. Gastric mucosal blood flow (GMBF) was measured by a laser Doppler flowmeter. Intravenous infusion of galanin dose-dependently inhibited the increase of acid secretion induced by pentagastrin and carbachol but not by histamine, without any influence on the GMBF response. Galanin also reduced basal acid secretion while increasing GMBF, but did not evoke any change in basal gastric alkaline secretion. M15, which is a galanin receptor antagonist in the central nervous system but acts as a full agonist in the gastrointestinal smooth muscle, also suppressed pentagastrin-induced acid secretion, similar to galanin. In addition, pentagastrin increased the release of histamine into the gastric lumen, and this response was significantly inhibited by galanin. These results suggest that the inhibitory effect of galanin on acid secretion is mediated by suppression of endogenous histamine release from enterochromaffin-like cells and that the process may be related to the activation of the same subtype of galanin receptors as in the central nervous system and pancreatic β-cells.

Distribution and kinetics of galanin infused into the ventral hippocampus of the rat: Relationship to spatial learning

A recent study has shown that ventral hippocampal galanin plays a role in spatial learning and that it has an inhibitory effect on basal acetylcholine release [Ögren S. O. et al. (1996) Neuroscience 75, 1127–1140]. The present studies were designed to compare the in vivo tissue distribution and kinetics of infused galanin (porcine) with the temporal effect of galanin on spatial learning in the rat. Daily bilateral microinfusions of galanin (1.5 nmol/side for five days) via chronic cannulae placed in the ventral hippocampus produced a significant impairment of acquisition of the spatial task when infused 20 min, but not 5 or 60 min, before the daily training session. No overall impairment of memory retention (examined 24 h after the last training session) was observed in the galanin-treated rats. These results indicate that galanin given in the ventral hippocampus produces a time-dependent effect on acquisition. Using an antibody to porcine galanin and immunohistochemistry, galanin infused in the ventral hippocampus was found to be distributed mainly within the ventral part of the hippocampus and around the infusion site. The infused galanin was rapidly cleared from the extracellular space between 5 and 20 min after infusion. Five minutes after infusion of galanin, a number of cells in the ventral hippocampus, both within and outside the zone of extracellularly located galanin, showed a positive galanin-like immunoreactivity. These cells appear morphologically to be medium-sized neurons with a similar position as cells showing neuropeptide Y-like immunoreactivity. At 20 and 60 min after infusion of galanin, no cells with detectable levels of galanin-like immunoreactivity could be seen. These results indicate that the temporal kinetics and distribution of infused galanin are of major importance for its behavioural effect in the ventral hippocampus. The rapid clearance of the infused galanin and its internalization by neuronal endocytotic mechanisms may be important for its effect on cognition.

Modulation by Galanin of Growth Hormone and Gonadotropin Secretion from Perifused Pituitary and Median Eminence of Prepubertal Male Calves

Galanin is widely distributed in the peripheral and central nervous system and has been indicated as a putative hypothalamic-hypophysiotropic hormone. This study was performed to investigate the effects of galanin on both growth (GH) and luteinizing hormones (LH) from pituitaries of young male calves. Pituitary slices (P, 500 microm in thickness) were perfused alone or coincubated with median eminence terminals (ME) in DMEM-F12 plus BSA 0.1% and antibiotics. The perifusion chambers were kept in equilibrium for 150 min, and medium samples were collected every 10 min for 240 min and stored at -20 degrees C until the measurement of LH and GH levels. Basal GH release increased up to 60% after galanin infusion (p < 0.01 vs. baseline levels) for 60 min in P alone; in P + ME coincubation, galanin-stimulated GH secretion was further increased by up to 200%. Basal LH release in chambers with P was significantly increased (up to 25%; p < 0.05) for 70 min after galanin infusion; P + ME coincubation showed a galanin-mediated increase in LH release of up to 50%. GH and LH responsiveness to exogenous GH-releasing hormone and gonadotropin-releasing hormone was not significantly modulated by galanin in our experimental model. In conclusion, galanin is demonstrated to have a significant stimulatory role in the secretion of GH and LH, with a combined action at both the hypothalamic and pituitary levels. ......................

Evidence that galanin is a parasympathetic, rather than a sympathetic, neurotransmitter in the baboon pancreas

To determine whether galanin is a pancreatic sympathetic neurotransmitter regulating insulin secretion in the baboon, as it is in the dog, we evaluated galanin for inhibitory effects on insulin secretion in conscious baboons, determined if baboon pancreatic islets are innervated by galaninergic fibers using immunohistochemistry, and measured galanin content in the major sympathetic ganglion supplying the pancreas. Surprisingly, infusion of galanin (1 μg/kg per min) had no effect on arginine-stimulated secretion of either insulin (71 ± 14 vs. 88 ± 17 μU/ ml; P = NS) or glucagon (104 ± 12 vs. 94 ± 9 pg/ ml; P = NS). By contrast, growth hormone secretion was markedly increased during galanin infusion. In the baboon celiac ganglion, no galanin immunoreactivity was detectable in sympathetic neuronal cell bodies by immunostaining and their content of galanin-like immunoreactivity, determined by radioimmunoassay, was only 3% of that in dog celiac ganglion (5.2 ± 0.8 vs. 158 ± 13 pmol/g; P < 0.001). By contrast, galanin immunoreactivity was observed in many nerve fibers in the baboon exocrine pancreas and occasionally in baboon pancreatic islets. Moreover, galanin content of the baboon pancreas was similar to that of dog (8.7 ± 1.5 vs. 5.5 ± 1.2 pmol/g; P = NS). The finding of galanin immunoreactivity in many neuronal cell bodies in baboon intrapancreatic ganglia suggests a parasympathetic source for these galaninergic fibers in the baboon. Together these data demonstrate that galanin is likely to be a parasympathetic neurotransmitter in the baboon pancreas, without major effects on insulin or glucagon secretion.

Activation of locus coeruleus somatostatin receptors induces an increase of growth hormone release in male rats.

Noradrenergic neurons of the locus coeruleus (LC) negatively regulate the endogenous rhythmicity of growth hormone (GH) secretion. These neurons express high concentrations of receptors for somatostatin (SRIH) and galanin (GAL), two neuropeptides which can affect electrical activity of LC neurons and also centrally modulate plasma GH levels. We thus investigated whether somatostatin and galanin receptors located in the LC are involved in GH regulation. Pulsatile patterns of endogenous GH secretion were monitored after unilateral infusion of the peptides into the lateral ventricle (ICV) or into the LC, after lesion of contralateral LC neurons by 6 hydroxydopamine. Neither unilateral LC lesions nor administration of saline affected GH release. When administered ICV, both SRIH (5 micrograms/microliter/15 min) and GAL (1 microgram/microliter/15 min) resulted in a marked increase in GH secretion. Infusion of SRIH into the LC induced a significant but weaker stimulation of plasma GH as compared to ICV injections. In contrast, infusion of GAL into the LC was ineffective. These results indicate that somatostatin can exhibit direct effects on noradrenergic neurons of the LC involved in GH regulation, whereas central effects of galanin on the hormone are mediated by distinct structures.

Galanin inhibits the vasodilatatory basalocortical cholinergic system in the anaesthetized rat.

In order to test the putative interaction between galanin and the vasodilatatory basalocortical cholinergic system, anaesthetized ventilated rats received a microinjection into the substantia innominata of 0.9% NaCl, 50 nmol carbachol, 50 nmol carbachol and 200 ng galanin, or 200 ng galanin. Cerebral blood flow (CBF) was measured with [14C]iodoantipyrine by the tissue sampling technique immediately following the intracerebral infusions. Under coinjection conditions, the flow increases observed after carbachol microinjection in the ipsilateral temporal and frontoparietal cortices were found to be significantly reduced (-37%, p < or = 0.02 and -25%, p < or = 0.05 respectively) compared with carbachol stimulated rats. The infusion of galanin by itself had no effect on CBF. These results demonstrate that galanin inhibits the vasodilatatory basalocortical cholinergic system and thus may possibly influence CBF by indirect mechanisms.

Effect of galanin on basal and stimulated secretion of prolactin, gonadotropins, thyrotropin, adrenocorticotropin and cortisol in humans.

Galanin enhances both baseline and growth hormone-releasing hormone (GHRH)-induced GH secretion both in animals and in man. Although galanin has a clear influence on the secretion of other anterior pituitary hormones in animals, in man it increases prolactin (PRL) slightly but does not affect spontaneous thyrotropin (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) or adrenocorticotropin (ACTH) secretion. The aim of our study was to verify the effect of galanin on basal and releasing hormone-stimulated release of gonadotropins, PRL, TSH, ACTH and cortisol secretion. As GH release has been shown to be inhibited by corticotropin-releasing hormone (CRH), we also studied the effect of CRH on galanin-stimulated GH increase. The effect of porcine galanin (15 micrograms/kg iv infused in 60 min) alone and in combination with thyrotropin-releasing hormone (TRH, 200 micrograms iv bolus), CRH (100 micrograms iv bolus) and gonadotropin-releasing hormone (GnRH, 100 micrograms iv bolus) on GH, PRL, TSH, ACTH, cortisol, FSH and LH secretion in seven normal young women (aged 25-30 years) was studied. Galanin infusion caused an increase in serum GH levels (p < 0.02) but failed to modify significantly the spontaneous PRL, LH, FSH, TSH, ACTH and cortisol secretion. The combined administration of TRH, GnRH and CRH caused a significant increase in PRL (p < 0.02), LH (p < 0.02), FSH (p < 0.02), TSH (p < 0.02), ACTH (p < 0.02) and cortisol (p < 0.05), but not in GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of galanin in the regulation of somatotrope and gonadotrope function in young ovulatory women

The aim of the study was to elucidate the role of the neuropeptide galanin in the regulation of somatotropic and gonadotropic function in normal women. Thirteen normally ovulating (aged 28 to 40 years), non-obese (body mass index, 18.4 to 27.1 kg/m 2) women with infertility due to a tubal or male factor were studied. Each woman underwent three tests: (1) bolus intravenous (IV) injection of growth hormone (GH)-releasing hormone (GHRH) (1–29)NH 2 1 μg/kg plus gonadotropin-releasing hormone (GnRH) 100 μg at time 0; (2) IV infusion of porcine galanin 500 μg in 100 mL saline from −10 minutes; and (3) bolus IV injection of GHRH(1–29)NH 2 1 μg/kg plus GnRH 100 μg at time 0 plus IV infusion of porcine galanin 500 μg in 100 mL saline from −10 to +30 minutes. All results are expressed as the mean ± SEM. GH peak after GHRH was 14 ± 5 μg/L; porcine galanin significantly increased serum GH (GH peak, 7.3 ± 1.2) with respect to baseline levels. No significant differences were observed between either GH peak or GH absolute values after galanin as compared with GHRH alone. Porcine galanin significantly enhanced GH response to GHRH (peak, 31.4 ± 4.4μg/L) with respect to either GHRH or galanin alone. Luteinizing hormone (LH)/folliclestimulating hormone (FSH) peaks after GnRH were 16.5 ± 5.3 and 17.4 ± 4 IU/L, respectively. Porcine galanin did not cause significant increases in serum LH and FSH levels with respect to baseline. Galanin coadministration slightly increased LH (peak, 25 ± 6.9 IU/L) but not FSH (peak, 17.1 ± 3.2) maximal responses to GnRH. In conclusion, galanin plays a significant role in the regulation of GH secretion in women, as well as in men. Moreover, this report suggests a minor role of galanin in the regulation of the hypothalamic-pituitary-ovarian axis in women.

Characterization of the paradoxical growth hormone inhibitory effect of galanin in acromegaly.

Galanin is a 29-amino acid straight-chain biologically active peptide which has been found to decrease circulating GH levels in some acromegalic patients, whereas is able to increase GH secretion in normal subjects. The aim of our study was to ascertain the incidence, entity and mechanism of the paradoxical GH inhibitory effect of galanin in acromegaly also looking at possible correlations between the GH responses to galanin and the main clinical and biochemical features of the patients. Finally, the effects of either successful or unsuccessful neurosurgical intervention on the GH inhibitory effect of galanin in acromegaly were investigated. A series of 23 consecutive patients with active acromegaly seen at the Endocrine Section of the Department of Internal Medicine of the University of Brescia (Italy) between 1991 and 1994 was examined. The acromegalic patients were subdivided in group 1 (i.e. patients who were 1) untreated, 2) evaluated before surgery, and 3) not cured after surgery and radiotherapy) and group 2 (i.e. surgically cured). All patients were submitted at least once to the following biochemical and radiological evaluations: 1) baseline serum insulin-like growth factor-I and PRL samples, 2) iv infusion of synthetic porcine galanin (500 micrograms in 100 mL saline) from -10 to 30 min, 3) iv bolus injection of TRH (200 micrograms) at time zero, 4) oral glucose tolerance test (75 g glucose, orally) at time zero, and 5) magnetic resonance of the pituitary sella. Adenomatous tissue obtained during neurosurgery in four patients was cultured in vitro, and the effect of the addition of galanin in the culture medium on GH secretion was tested. During galanin infusion in 19 of 21 group 1 patients, serum GH levels were lower with respect to baseline (range of GH decrease, -6.2 to -85.4% with respect to basal levels). During galanin infusion, no reductions in GH levels were observed in the acromegalic patients cured after neurosurgery (group 2); on the contrary, 6 of 7 patients displayed a normal stimulatory response to galanin (range of GH increase, +120-1533.3% of the basal level). A significant correlation between the percent decrease in GH levels after galanin treatment and the percent increase after TRH was found in group 1 patients (r = -0.783; P < 0.05). In three of the four adenomas examined, galanin determined a clear decrease in GH secretion (mean nadir, 63.3 +/- 12% of the baseline secretion rate). In conclusion, we demonstrated that the large majority of numerous patients with active acromegaly show a decrease in serum GH levels after galanin administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Galanin infusion restores the blunted GH responses to GHRH administration during GH treatment in children with constitutional growth delay

GH responses to GHRH (in basal conditions), GHRH (after six months of recombinant GH therapy) and GHRH plus galanin administration (after GH therapy) were determined in six children with constitutional growth delay (CGD). Before treatment, GHRH administration caused a clear rise of GH levels (mean GH peak: 38.0 +/- 7.2 ng/ml); mean GH net incremental area under the curve/120 min (GH nAUC) was 2631.0 +/- 519.8 ng/ml/120 min. During GH treatment, both height velocity and IGF-I levels significantly increased from 4.3 +/- 0.1 cm/yr to 9.4 +/- 0.9 cm/yr (p < 0.001) and from 218.7 +/- 12.3 ng/ml to 328.0 +/- 28.2 ng/ml (p < 0.001), respectively. After 6 months of GH therapy, mean GH peak (21.7 +/- 2.2 ng/ml) and mean GH nAUC (847.7 +/- 109.8 ng/ml/120 min) after GHRH administration were significantly lower (p < 0.05) than in basal conditions. Galanin infusion (10 micrograms/kg/bw) was able to completely restore the reduced GH responsiveness to GHRH administration. In fact, mean GH peak and mean GH nAUC after GHRH plus galanin were similar to those recorded after basal GHRH administration (GH peak: 37.5 +/- 4.0 ng/ml; GH nAUC: 2279.8 +/- 430.5 ng/ml/120 min). In conclusion, this study shows that the reduction of pituitary responsiveness to GHRH administration during GH treatment is not dependent on the depletion of the promptly GH releasable pool, since somatotroph refractoriness to GHRH can be overriden by the concomitant administration of galanin.

Differential effects of a graded selective suppression of insulin secretion with galanin on glucose production and removal in dogs.

The metabolic response to graded decreases in insulin concentration was evaluated by measuring the concentration, production, and metabolic clearance rate of glucose in response to the infusion of different galanin doses (1-12 micrograms/kg/h) in 18-h fasted dogs. Peripheral and portal concentrations of insulin and glucagon were measured simultaneously before, during, and after galanin infusions. No increases in portal or peripheral glucagon levels were seen at any dose of galanin infused but, in contrast, dose-dependent decreases of insulin levels occurred in both circulations. The metabolic clearance rate of glucose fell by approximately 25-30% at each dose of galanin infused; suggesting that the maximum effect was reached at the lowest dose. The rate of glucose production increased in a dose-dependent manner with integrated responses of 210 +/- 170, 620 +/- 80, 1,330 +/- 440, 1,920 +/- 310, 1,940 +/- 170, and 1,970 +/- 600 mg/kg at galanin doses of 1, 2, 4, 7, 10, and 12 micrograms/kg/h respectively; saturation of this response occurs at the 7 micrograms/kg/h dose of galanin. The changes in glucose production reflect most closely changes in the fractional decrease in insulin levels both in the portal and peripheral circulations. These changes appear to be mediated by insulin acting directly on the liver, because no alterations in the concentrations of the glucogenic substrates, lactate and glycerol, were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of pancreatic exocrine secretion by galanin.

The influence of extrapancreatic nerves on the inhibition of meal- and secretogogue-induced pancreatic secretion by galanin was studied in conscious dogs. Chronic pancreatic fistulae were created in five mongrel dogs and a second group of five dogs also underwent complete pancreatic denervation. After recovery, galanin dose response (150-1,200 pmol/kg/h) revealed that 600 pmol/kg/h was the lowest dose of galanin to significantly inhibit pancreatic exocrine secretion. Pancreatic responses to a mixed meal, cholecystokinin (CCK) dose response (12.5-200 ng/kg/h), and secretin dose response (16-500 ng/kg/h) were determined. The experiments were then replicated with a continuous background infusion of galanin (600 pmol/kg/h). Galanin inhibited meal-, CCK-, and secretin-induced bicarbonate outputs in both the innervated and denervated pancreas. Galanin also inhibited meal- and CCK-induced protein responses in both groups. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of galanin.

Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity

Acute central administration of galanin has been reported to increase fat consumption. These experiments were designed to test the hypothesis that repeated injections of galanin would elicit hyperphagia and weight gain and that this response would depend on the available diet. Male Sprague-Dawley rats were fed high (56% energy) or low (10% energy) fat diets. Galanin (300 pmol) or saline vehicle was injected into the third ventricle twice daily for 7 days and three times daily for another 6 days. On both the high-carbohydrate and high-fat diets, twice daily galanin increased daytime food intake, but there was a compensatory decrease in nighttime intake. The addition of a third, nighttime injection of galanin was ineffective in producing an increase in total 24-h intake. There was no significant increase in body weight during galanin treatment in rats eating either diet although animals eating the high-fat diet gained more weight as reflected by a significant increase in epididymal fat pad weight. Galanin treatment had no effects on serum insulin, glucose or corticosterone concentrations, measured at the end of the experiment. However, animals fed the high-fat diet had significantly higher insulin concentrations at the time of sacrifice. Although repeated central infusions of galanin reliably stimulated daytime intake of both diets, they failed to increase total daily energy intake or body weight.