Increased vasopressor potency of the centrally injected neuropeptide Y fragment 13-36 in the adult spontaneously hypertensive awake male rat of the Wistar-Kyoto strain.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
L F Agnati
Publications and source records attributed to L F Agnati.
On the role of neuropeptide Y in information handling in the central nervous system in normal and physiopathological states. Focus on volume transmission and neuropeptide Y/alpha 2 receptor interactions.
The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.
Aging↗
Neuropeptide Y and central cardiovascular regulation. Focus on its role as a cotransmitter in cardiovascular adrenergic neurons.
Explore the source record for details and available documents.
Adrenergic Fibers↗
Nigrostriatal dopamine neurons, D1 transmission in basal and ischemic states and protective effects of gangliosides.
Explore the source record for details and available documents.
Antibodies↗
Increased diffusion of prolactin-like material into the brain neuropil from homologous adenohypophyseal transplants in the rat neostriatum after a 6-OH-dopamine induced degeneration of the mesostriatal dopamine neurons.
Young adult female rats were used as donors and recipients of homologous adenohypophyseal transplants. The transplants were stereotaxically placed unilaterally into the intact and 6-hydroxy-dopamine (6-OH-DA) denervated neostriatum. In the 6-OH-DA-denervated neostriatum the zone of prolactin-like immunoreactivity was increased in the neuropil surrounding the adenohypophyseal transplant compared with that in the non-denervated neostriatum. These results indicate that the loss of neostriatal dopamine leads to an increase in prolactin release from the adenohypophyseal striatal transplant giving further evidence for the existence of volume transmission in brain.
Animals↗
Pertussis toxin treatment counteracts intramembrane interactions between neuropeptide Y receptors and alpha 2-adrenoceptors.
The effect of intracerebroventricular injections of pertussis toxin were investigated on the neuropeptide Y-induced modulation of alpha 2-adrenoceptor binding in membranes from the dorsomedial medulla oblongata of the rat. Concentration-response experiments showed that neuropeptide Y reduced the binding affinity of the alpha 2-agonist, p-[3H]aminoclonidine, with a maximal effect of 30% at 3-30 nM. Pertussis toxin treatment (10 micrograms, 24 h) counteracted this modulation, without reducing the binding of neuropeptide Y to its own receptor. The results indicate that pertussis toxin-sensitive G-proteins are essential for the mediation of the intramembrane interaction between neuropeptide Y receptors and alpha 2-adrenoceptors.
Adenosine Diphosphate Ribose↗
Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum.
Microdialysis in the neostriatum of the halothane-anesthetized male rats was used to study the effect of neurotensin on the release of dopamine and its metabolites in the absence or presence of systemic apomorphine treatment. Perfusate levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assayed by high-performance liquid chromatography in combination with electrochemical detection. Perfusion with neurotensin (1000 nM but not 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC and HVA. Systemic treatment with apomorphine (0.05 and 0.5 mg/kg, s.c.) reduced the dialysate levels of dopamine, DOPAC and HVA in a dose-related way. Neurotensin (10 nM but not 1 nM) counteracted the inhibitory effect of apomorphine on dialysate levels of dopamine without affecting those of DOPAC and HVA. The results indicate a facilitatory effect of neurotensin on dopamine release in rat neostriatum. It is suggested that activation of neurotensin receptors may cause a reduction in the affinity of dopamine autoreceptors, since the low dose of neurotensin is able to counteract the inhibitory effect of apomorphine on dopamine release.
3,4-Dihydroxyphenylacetic Acid↗
Acute treatment with clozapine blocks D1 dopamine receptor binding in discrete brain areas of the male rat.
The ability of acute treatment with clozapine in vivo to block D1 receptors in the rat telencephalon and midbrain was investigated using the irreversible inactivation of [125I]SCH 23982 binding sites by N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 6 mg/kg, i.p., 24 h). As analyzed by quantitative autoradiography, clozapine (40 mg/kg, i.p., 15 min before EEDQ administration) was found to produce a partial protection of central D1 receptors in all brain areas investigated, including cerebrocortical regions. These data could perhaps explain the failure of clozapine to induce tardive dyskinesia upon chronic treatment.
Animals↗
Transient forebrain ischemia produces multiple deficits in dopamine D1 transmission in the lateral neostriatum of the rat.
Striatal dopamine D1 transmission was studied in rats 7 days after transient (30 min) forebrain ischemia using the 4-vessel occlusion model. The striatal distribution of dopamine D1 ([3H]SCH 23390 binding sites) and D2 ([3H]sulpiride binding sites) receptors as well as the distribution of adenylate cyclase ( [3H]forskolin binding sites) and of the intracytoplasmic dopamine and cAMP-regulated phosphoprotein DARPP-32 related to D1 transmission were analyzed. While the distribution of D2 receptors was unaffected 7 days after the ischemic insult, all the other markers showed a patchy disappearance in the dorsolateral part of the neostriatum. These findings underline the existence of selective multiple deficits in D1 transmission after transient forebrain ischemia in rat striatum.
Animals↗
Pertussis toxin treatment counteracts the cardiovascular effects of neuropeptide Y and clonidine in the awake unrestrained rat.
The role of G-proteins in the mediation of the cardiovascular effects of neuropeptide Y and the alpha 2-adrenoceptor agonist clonidine was investigated by injections of pertussis toxin (10 micrograms/30 microliters, i.v.t., 24 h) in the awake unrestrained male rat. Treatment with pertussis toxin was found to inhibit the hypotensive and bradycardic actions of neuropeptide Y (1250 pmol) and the hypotensive actions of clonidine (1875 pmol). Control experiments showed that treatment with pertussis toxin caused an approximately 50% reduction in the back-ADP-ribosylation of GTP-binding proteins. These results suggest that G-proteins mediate the central cardiovascular actions of neuropeptide Y and clonidine.
Animals↗
Evidence for the existence of a population of arcuate neurons costoring choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the male rat.
By combined immunoperoxidase and immunofluorescence histochemistry we have analyzed the distribution of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunoreactive (IR) perikarya within the same sections of the mediobasal hypothalamus of the male rat. Evidence was obtained for the existence of perikarya costoring TH and ChAT immunoreactivities in both the dorsomedial and ventrolateral part of the arcuate nucleus and in the adjacent periarcuate nucleus at all rostrocaudal levels. The results strongly implicate interactions between dopamine and acetylcholine as well as acetylcholine and growth hormone releasing factor in dorsomedially and ventrolaterally located TH/ChAT costoring tuberoinfundibular neurons, respectively.
Animals↗
Neuropeptide Y increases the inhibitory effects of clonidine on potassium evoked 3H-noradrenaline but not 3H-5-hydroxytryptamine release from synaptosomes of the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat.
The release of 3H-noradrenaline (3H-NA) and of 3H-5-hydroxytryptamine (3H-5-HT) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat using a superfusion apparatus. Based on concentration-response curves obtained by analyzing the full-time course of the inhibitory effects of clonidine on 3H-NA and on 3H-5-HT release neuropeptide Y (NPY) (1 nM) was shown to significantly increase the ability of clonidine to inhibit 3H-NA release in synaptosomes isolated from the hypothalamus and from the frontoparietal cortex. NPY (1 nM) alone had no effect on K+-evoked 3H-NA release from these regions. In contrast, NPY (1 nM) did not modulate the inhibitory effects of clonidine on 3H-5-HT release in the above mentioned regions. These results indicate that NPY can increase the sensitivity of the alpha 2-autoreceptors belonging to hypothalamic NA and/or to adrenaline nerve terminals and to cortical NA nerve terminals, while the alpha 2-heteroreceptors inhibiting 3H-HT release in the same brain regions appear not to be regulated by high affinity NPY receptors. Thus, alpha 2-autoreceptors and alpha 2-heteroreceptors appear to be differentially controlled by high affinity NPY receptors at least with regard to regulation of 3H-NA and 3H-5-HT release, respectively.
Animals↗
Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat.
Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Reduced inhibitory effects of clonidine and neuropeptide Y on 3H-noradrenaline release from synaptosomes of the medulla oblongata of the spontaneously hypertensive rat.
The release of 3H-noradrenaline (3H-NA) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto and spontaneously hypertensive male rat (14 weeks old) using a superfusion apparatus. Based on concentration-response curves clonidine was shown to have a reduced ability to inhibit 3H-NA release in synaptosomes isolated from the spontaneously hypertensive rat (SHR) versus the normotensive rat. Furthermore, only a high concentration of NPY (100 nM) had the ability to enhance the inhibitory effects of clonidine on 3H-NA release in synaptosomes isolated from the medulla oblongata of the SH male rat, while 1 nM of NPY was effective in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto rat. These results may indicate a reduced presynaptic alpha 2-adrenoceptor and NPY receptor function to inhibit 3H-NA release from NA and/or adrenaline (A) nerve terminals in the medulla oblongata of the adult 14 weeks old SHR.
Animals↗
Neuroendocrine actions of nicotine and of exposure to cigarette smoke: medical implications.
Over many years a large number of studies have demonstrated that nicotine and exposure to cigarette smoke produce marked neuroendocrine changes in animals and in man. The initial effects of nicotine are characterized by a marked hypersecretion of ACTH, vasopressin, beta-endorphin, prolactin and LH. Many of these very acute stimulatory effects of nicotine rapidly disappear, probably due to a desensitization of the central nicotinic cholinergic receptors involved. Instead, upon acute intermittent treatment with nicotine or exposure to cigarette smoke, an inhibition of prolactin, LH and TSH secretion occurs, which is associated with maintained hypersecretion of corticosterone. These effects are probably mediated via activation of central cholinergic receptors of the ganglionic type. Evidence indicates that the inhibitory effects of nicotine on LH and prolactin secretion are produced via an activation by these nicotinic receptors of the tubero-infundibular dopamine neurons, releasing dopamine as a prolactin inhibitory factor. Dopamine inhibits LHRH release via an axonic interaction involving D1-like dopamine receptors in the median eminence. It therefore seems possible that the reduced fertility found in heavy smokers may be counteracted by D1 receptor antagonists. The symptoms associated with glucocorticoid hypersecretion induced by nicotine is discussed considering not only the peripheral side effects but also permanent deficits in hippocampal glucocorticoid receptors and loss of hippocampal neurons. In view of the important influence of hormones on immune functions, it seems likely that smoking will cause disturbances in immune responsiveness. Finally, the nicotine-induced alterations of neuroendocrine function, especially in the pituitary-adrenal axis and in vasopressin release, may also lead to behavioural consequences in smokers, especially in the withdrawal phase.
Animals↗
Neurochemical mechanisms underlying the neuroendocrine actions of nicotine: focus on the plasticity of central cholinergic nicotinic receptors.
Explore the source record for details and available documents.
Animals↗
Protective effects of chronic nicotine treatment on lesioned nigrostriatal dopamine neurons in the male rat.
The present results demonstrate that chronic nicotine treatment can in part protect against mechanically-induced and neurotoxin-induced degeneration of nigrostriatal DA neurons. These results indicate that in sufficient doses chronic treatment with nicotine may be considered in the pharmacological treatment of Parkinson's disease. It remains to be demonstrated whether these protective actions can be extended to include also other injured neurons such as the cholinergic neurons, known to be severely affected in Alzheimer's disease.
Animals↗
Regional differences in glucocorticoid receptor immunoreactivity among neuropeptide Y immunoreactive neurons of the rat brain.
By means of two-colour immunocytochemistry using a mouse monoclonal antibody directed against the rat liver glucocorticoid receptor (GR) and a rabbit polyclonal neuropeptide Y (NPY) antiserum combined with the biotin-avidin immunoperoxidase and a double immunofluorescence procedure, it has been possible to demonstrate nuclear GR immunoreactivity (IR) in neurons showing cytoplasmatic NPY IR in rat brain. The majority of NPY immunoreactive perikarya of the medial parvocellular part of the arcuate nucleus, locus coeruleus and the rostral and caudal part of the ventrolateral medulla oblongata contained strong nuclear GR IR. Many of the NPY immunoreactive neurons present in the subnuclei of the nucleus tractus solitarius also contained nuclear GR IR, while most of the NPY immunoreactive perikarya of the cerebral cortex and all of the neostriatum appeared to lack GR IR. These results indicate that NPY immunoreactive neurons in the upper and lower brain stem, but not in the cerebral cortex and in the neostriatum may be directly involved in mediating central effects of glucocorticoids.
Animals↗