Galanin and its three receptors in human pituitary adenoma

Tofighi, Roshan; Barde, Swapnali; Palkovits, Miklós; Höög, Anders; Hökfelt, Tomas; Ceccatelli, Sandra; Al, Hulting

doi:10.1016/j.npep.2012.07.003

Cited by 7 publications

(18 citation statements)

References 41 publications

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“…Again, qPCR results indicate very low GalR1 levels. As a note, GalR2 and -3 have a high degree of homology; therefore in a previous study we demonstrated the specificity of the primers for the two receptors (114).…”

Section: Significancementioning

confidence: 66%

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Maître

Barde

Palkovits

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Using riboprobe in situ hybridization, we studied the localization of the transcripts for the neuropeptide galanin and its receptors (GalR1-R3), tryptophan hydroxylase 2, tyrosine hydroxylase, and nitric oxide synthase as well as the three vesicular glutamate transporters (VGLUT 1-3) in the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) regions of postmortem human brains. Quantitative real-time PCR (qPCR) was used also. Galanin and GalR3 mRNA were found in many noradrenergic LC neurons, and GalR3 overlapped with serotonin neurons in the DRN. The qPCR analysis at the LC level ranked the transcripts in the following order in the LC: galanin >> GalR3 >> GalR1 > GalR2; in the DRN the ranking was galanin >> GalR3 >> GalR1 = GalR2. In forebrain regions the ranking was GalR1 > galanin > GalR2. VGLUT1 and -2 were strongly expressed in the pontine nuclei but could not be detected in LC or serotonin neurons. VGLUT2 transcripts were found in very small, nonpigmented cells in the LC and in the lateral and dorsal aspects of the periaqueductal central gray. Nitric oxide synthase was not detected in serotonin neurons. These findings show distinct differences between the human brain and rodents, especially rat, in the distribution of the galanin system and some other transmitter systems. For example, GalR3 seems to be the important galanin receptor in both the human LC and DRN versus GalR1 and -2 in the rodent brain. Such knowledge may be important when considering therapeutic principles and drug development.he locus coeruleus (LC) and the dorsal raphe nucleus (DRN)/raphe median nucleus (MRN) have been the focus of clinical and preclinical monoamine research for almost half a century. Using the formaldehyde fluorescence (Falck-Hillarp) method (1), Dahlström and Fuxe (2) originally described these nuclei in the rat as containing noradrenaline (NA) (the A6 group) and 5-hydroxytryptamine (5-HT; serotonin) (the B7/8 groups), respectively. The LC harbors 2,800-3,600 neurons with an additional 260 neurons in the subcoeruleus area, the great majority of which are noradrenergic (3-6).The DRN forms a rostro-caudal, ventral midline column and is part of the periaqueductal central gray (PAG) (7) with a large number of 5-HT neurons that can be subdivided into several subgroups (2,(8)(9)(10)(11). Both the NA-LC (5, 6, 12) and the 5HT-DRN (8-11, 13) neurons have wide projections to most forebrain areas.In humans the LC is a compact, blue-pigmented nucleus consisting of a total of ∼50,000 neurons (both sides), almost all of which are noradrenergic (14-16). The DRN comprises about 165,000 5-HT neurons, which constitute around 70% of all DRN neurons (17). Thus, there are numerous nonserotonergic neurons in the human DRN, as is also the case in other species, including the mouse (18,19).It now is well established that most neurons synthesize and release several types of messenger molecules in the process known as "cotransmission" (20-26). For example, in the rat some serotonergic DRN neurons synthesize nitric oxide (NO), visualized as N...

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Section: Significancementioning

confidence: 66%

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Maître

Barde

Palkovits

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Analysis of human HNSCC revealed significantly increased GAL 3 expression in the tumors compared with normal tissue (Sugimoto et al, 2009). Similarly, GAL 3 expression was detected in human pituitary adenomas associated with tumor relapse, whereas it was absent in postmortem pituitaries (Tofighi et al, 2012). These data suggest a role for GAL 3 in cancer biology and support the idea that, like GAL 2 , this galanin receptor deserves further experimental investigation, not only as a potential diagnostic tool but as a drug target to modify the activity of certain tumor types, particularly as a specific GAL 3 antagonist (SNAP-37889) is available.…”

Section: Cancermentioning

confidence: 85%

“…Increased GAL 1 expression was also observed in human pituitary adenomas relative to levels in normal human pituitaries (Tofighi et al, 2012), suggesting cancer-promoting properties for GAL 1 , at least in these tumors. Recently, GAL 1 was proposed to contribute to resistance to chemotherapeutic drugs in colon cancer, because GAL 1 silencing led to enhanced chemosensitivity of human colon cancer cell lines (Stevenson et al, 2012).…”

Section: Cancermentioning

confidence: 92%

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Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

Lang

Gundlach

Holmes

et al. 2015

Pharmacological Reviews

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276

310

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“…G protein coupled receptors (GPCRs) are of crucial importance in modern pharmacotherapies and neurosciences, a fact explained by the high amount of functions, diseases and disorders that involve GPCRs or their linked pathways including enzymes, second messengers (Barreda-Gómez et al, 2005Duttlinger et al, 2003;Ghanemi and Hu, 2014;Hibert et al, 1994;Hofmann et al, 2013;Lin et al, 2011;Moser and Klose, 1993;Shen et al, 2013;Tofighi et al, 2012;Wirz et al, 2005) which, all, constitute potential targets in pharmacology and also in experimental biology to modify, stimulate or inhibit the signal transduction with or without the receptors activation. Therefore, investigating the properties of the GPCRs will without doubt lead to more advances towards clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Elements toward novel therapeutic targeting of the adrenergic system

Ghanemi

2015

Neuropeptides

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Galanin and its three receptors in human pituitary adenoma

Cited by 7 publications

References 41 publications

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

Elements toward novel therapeutic targeting of the adrenergic system

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