Role of galanin and galanin(1-15) on central cardiovascular control.

Galanin and the N-terminal fragment Galanin(1-15) are involved in central cardiovascular regulation. The present paper reviews the recent cardiovascular results obtained by intracisternal injections of Galanin and Galanin(1-15) showing that: (A) the Galanin antagonist M40 blocks the central cardiovascular responses induced by Galanin(1-15) but not those elicited by Galanin; (B) both Galanin and Galanin(1-15) induce the expression of c-Fos in cardiovascular nuclei of the medulla oblongata with different temporal and spatial profiles; (C) the cardiovascular action of Galanin(1-15), but not Galanin, is mediated by peripheral beta-receptor stimulation; (D) and it is demonstrated an antagonistic Galanin/alpha2-adrenoceptors interaction as well as a differential modulation of central cardiovascular responses of Angiotensin II by Galanin or Galanin(1-15). All these data strengthen the involvement of both Galanin molecules as neuromodulators on central cardiovascular regulation.

Prolonged effects of intraventricular galanin on a 5-hydroxytryptamine(1A) receptor mediated function in the rat.

Galanin (3 nmol/rat), 2 h after its intracerebroventricular (i.c.v.) administration to male rats, attenuated the passive avoidance (PA) retention deficit induced by the 5-hydroxytryptamine (HT)(1A) receptor agonist 8-hydroxy-2-(di-N-propylamino)tetraline (8-OH-DPAT) (0.2 mg/kg) The reduction in the postjunctional 5-HT(1A) receptor-mediated response after i.c.v. galanin was not associated with changes in the mRNA levels and agonist binding properties of cortical limbic 5-HT(1A) receptors, believed to be the target receptors mediating the PA deficit caused by 8-OH-DPAT. These results suggest that acute increases of galanin transmission in vivo even after 2 h can counteract limbic 5-HT(1A) receptor-mediated responses of relevance for affective disorders without significantly affecting gene expression and binding characteristics of cortical limbic 5-HT(1A) receptors.

Internalization of intracerebrally administered porcine galanin (1-29) by a discrete nerve cell population in the hippocampus of the rat.

In spite of numerous studies utilizing intraventricular administration of porcine galanin (1-29), little is known about the spread and cellular distribution of exogenous galanin following intraventricular administration. In this study a discrete nerve cell body population with their dendrites became strongly galanin immunoreactive (IR) in the dorsal hippocampus following intraventricular porcine galanin (1.5 nmol/rat). Time course experiments showed that after time intervals of 10 and 20 min, but not at 60 min, scattered small- to medium-sized galanin-IR nerve cell bodies and their dendrites were present in all layers of the dorsal and ventral hippocampus. In double-immunolabeling experiments most of these nerve cells were identified as putative GABA interneurons costoring NPY-IR or somatostatin-IR in some cases. Twenty minutes after intraventricular injection of artificial cerebrospinal fluid (aCSF), only endogenous punctate and coarse galanin-IR terminals were found, but no galanin-IR cell bodies. Intrahippocampal injection of fluorophore-labeled galanin resulted in the appearance of fluorescent nerve cell bodies with the same morphology and localization as in the above experiments. Coadministration of the putative galanin antagonist M35 (0.5 nmol) and galanin (1.5 nmol) resulted in a reduced number of galanin-IR nerve cell bodies in the hippocampus of half of the rats. These findings support the existence of a population of putative hippocampal GABA interneurons with the ability to internalize and concentrate galanin and/or its fragments present in the extracellular fluid, possibly mediated by galanin receptors.

Intraventricular galanin produces a time-dependent modulation of 5-HT1A receptors in the dorsal raphe of the rat.

Galanin given i.c.v. increased the K(D) values of 5-HT1A receptors in the DR by 100% 10 min after administration. This effect had disappeared 2 h and 5 h after galanin administration. In contrast, i.c.v. galanin caused a 40% increase in the Bmax values at 2 h without affecting the Bmax values 10 min and 5 h after i.c.v. galanin. The mRNA levels of 5-HT1A receptors and of galanin in the DR were significantly decreased by 33% and 56% respectively 2h but not 5h after i.c.v. galanin. These results suggest that in vivo galanin can modulate somatodendritic 5-HT1A receptors in the DR in a time-dependent manner via galanin-5-HT1A receptor interactions. The findings implicate a potential role of galanin in affective disorders.

Galanin and learning.

A number of studies indicate that galanin (GAL) is a potent modulator of basal acetylcholine release in the rat forebrain e.g. in the cholinergic neurons of the septo-hippocampal projections. Thus, GAL perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. This finding indicates that GAL may act via different mechanisms within the subsystems of the hippocampus. This hypothesis has received support from studies using the Morris swim maze, a learning task dependent on hippocampal mechanisms. GAL (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate when injected into the dorsal hippocampus. However, the effects of GAL on acetylcholine release and on spatial learning, which are due to activation of GAL-receptors, appear to be indirectly mediated possibly via noradrenaline transmission. GAL is also a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. These findings are discussed in relation to the role of acetylcholine and serotonin in cognition.

Intraventricular galanin modulates a 5-HT1A receptor-mediated behavioural response in the rat.

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.

Estrogen down-regulates mRNA encoding the exocytotic protein SNAP-25 in the rat pituitary gland.

Exocytosis is dependent on specific proteins that are located at the secretory granule membrane, in the cytoplasm or at the plasma membrane. The mRNA expression of synaptosomal-associated protein of 25 kDa (SNAP-25) isoforms SNAP-25a and SNAP-25b, vesicle associated membrane protein (VAMP) 2, mammalian homologue of unc-18 (munc-18) and Hrs-2 was studied in the pituitary of ovariectomized rats after subcutaneous insertion of capsules containing estrogen or placebo using in situ hybridization. Estrogen treatment (0.25 mg estradiol) significantly decreased SNAP-25a (32%; 10%) and SNAP-25b (25%; 22%) mRNA levels in the anterior and intermediate lobes, respectively, whereas VAMP-2, munc-18 and Hrs-2 mRNA levels remained unchanged. The results suggest that estrogen selectively regulates SNAP-25 transcription in the pituitary gland, but leaves VAMP-2, munc-18 and Hrs-2 mRNA levels unaffected.

Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain.

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.

5-HT1A receptor activation: short-term effects on the mRNA expression of the 5-HT1A receptor and galanin in the raphe nuclei.

Systemic administration of the 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 0.3 mg/kg, s.c.) was used to explore the effects of activation of 5-HT1A receptors on expression of mRNA coding for 5-HT1A receptor, tryptophan hydroxylase (TPH) and galanin in the ascending raphe nuclei. 8-OH-DPAT increased the hybridization signal of the 5-HT1A receptor by 105% in the dorsal raphe nucleus (B7) 30 min after the injection. No effects were seen at the later time points (2-8 h). In the median raphe nucleus (B8) and the B9 cell group in the medial lemniscus, 8-OH-DPAT induced a marked decrease in labeling 30 min after injection. At 8 h following 8-OH-DPAT injection, the effect had shifted to an increase in 5-HT1A receptor labeling by 68% in the B8 area. Importantly 8-OH-DPAT had no significant effects on the expression of mRNA coding for TPH and galanin. The results suggest an important and differential mechanism for the regulation of 5-HT1A receptor mRNA levels in the dorsal and median raphe nuclei. This regulation may be of importance for the differential control of the activity of the ascending 5-HT neurons, and hence for mood regulation. The results also indicate a dissociation between the effects mediated by 5-HT1A receptor functions and those regulating the coexisting peptide galanin in the dorsal raphe.

Critical daylength and temperature level for photoperiodism in gonadal maturation of goldfish.

When yearling goldfish were exposed to 12, 13, 14, 15 or 16 L at 24 degrees C from 27 October-27 December, females were suppressed at 12 or 13 L but matured to spawn at other daylengths. The critical daylength was thus located at 13-14 L. Males were not suppressed at any daylength, and spermiated to pass quickly into the post-spawning stage, commencing the next maturation cycle after completion of the regressive stage. When exposed to 12 or 16 L at 18 or 21 degrees C from 5 December-5 March, a few females matured and spawned at 21 degrees C/12 L, while most females did so on other regimes. The temperature level, below which the photoperiodic response became indistinct, was between 18 degrees and 21 degrees C. Most males continued spermatogenesis at 18 degrees C/16 L, but they spermiated and passed into the post-spawning stage quickly on other regimes.