Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception

Dobolyi, Árpád; Ueda, Hiroshi; Uchida, Hitoshi; Palkovits, Miklós; Usdin, Ted B.

doi:10.1073/pnas.042416199

Cited by 71 publications

(116 citation statements)

References 44 publications

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“…The expression of TIP39 in the central nervous system is restricted to two major sites, the subparafascicular area in the caudal thalamus and the medial paralemniscal nucleus in the lateral pons (Dobolyi et al, 2003b;Dobolyi et al, 2002). The distributions of TIP39 fibers (Dobolyi et al, 2003b) and the PTH2 receptor in the central nervous system have recently been described in young male rats.…”

Section: Introductionmentioning

confidence: 99%

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Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Dobolyi

Wang

Irwin

et al. 2006

J of Comparative Neurology

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Tuberoinfundibular peptide of 39 residues (TIP39) is a selective agonist of the parathyroid hormone 2 (PTH2) receptor. The topographical distributions of TIP39 and the PTH2 receptor in the brain, described in young male rats, suggested that TIP39 has limbic and endocrine functions. In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR and immunocytochemistry. TIP39's distribution and expression levels are similar in young female and male brains. TIP39 mRNA levels peak at postnatal day 14 and subsequently decline both in the subparafascicular area and the medial paralemniscal nucleus, the two major sites where TIP39 is synthesized. A greater developmental decrease in TIP39 expression in males leads to greater levels in older females than older males. The decrease is partially reversed by pre-pubertal but not post-pubertal gonadectomy. TIP39 peptide levels in cell bodies change in parallel with mRNA levels, while TIP39 appears and disappears somewhat later in nerve fibers. In addition, TIP39 peptide levels are also sexually dimorphic in older rats. In contrast, PTH2 receptor expression in the brain does not decrease during puberty and is not sexually dimorphic even in old animals. The appearance of TIP39 during early, and decline during late, postnatal development together with the gender dependent levels in mature animals suggest that TIP39 may play a role in sexual maturation or gender specific functions. Indexing termstuberoinfundibular peptide of 39 residues; parathyroid hormone 2 receptor; TIP39 and PTH2 receptor in situ hybridization and immunocytochemistry and quantitative

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Section: Introductionmentioning

confidence: 99%

“…Mouse, rat, human and zebrafish sequences have been reported (Dobolyi et al, 2002;Hansen et al, 2002;John et al, 2002;Papasani et al, 2004). TIP39 has limited common sequence with parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) and a similar three-dimensional structure (Piserchio et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Dobolyi

Wang

Irwin

et al. 2006

J of Comparative Neurology

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“…Many of these regions process pain information. Central administration of TIP39 is pronociceptive (15), whereas the absence of TIP39 signaling, in TIP39 knockout (KO) mice, mice with null mutation of the PTH2R, or following acute PTH2R block, reduces nocifensive responses in animal models of acute thermal and inflammatory pain (11). In this study, we followed up on these observations by investigating the potential role of TIP39 signaling in chronic pain models.…”

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confidence: 99%

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Dimitrov

Kuo

Kohno

et al. 2013

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

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Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of α-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, α-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brainstem GABAergic interneurons that innervate noradrenergic neurons. TIP39's normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.supraspinal pain | allodynia | partial sciatic nerve ligation | Freund's adjuvant

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“…4), and human TIP39 gene expression is far more widespread. (29) Furthermore, ClustalW alignment showed that only 6 amino acids are identical in the two proteins (data not Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, fugu Pth-L does not contain this cleavage site, and the intron is present before an SRR motif. (30) More important, fugu Pth-L is capable of stimulating adenylate cyclase in sea bream scales, (30) whereas the elephant shark (29) suggesting that Pth2 may have a role in neurotransmission, in the neuroendocrine system, or as a neuromodulator. The presence of elephant shark Pth2 mRNA and protein in the spleen implies that it might have a role in the hemopoietic and/or immune systems.…”

Section: Discussionmentioning

confidence: 99%

Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

Liu¹,

Ibrahim²,

Tay³

et al. 2010

Journal of Bone and Mineral Research

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The development of bone was a major step in the evolution of vertebrates. A bony skeleton provided structural support and a calcium reservoir essential for the movement from an aquatic to a terrestrial environment. Cartilaginous fishes are the oldest living group of jawed vertebrates. In this study we have identified three members of the parathyroid hormone (Pth) gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii). The three genes include two Pth genes, designated as Pth1 and Pth2, and a Pthrp gene. Phylogenetic analysis suggested that elephant shark Pth2 is an ancient gene whose orthologue is lost in bony vertebrates. The Pth1 and Pth2 genes have the same structure as the Pth gene in bony vertebrates, whereas the structure of the Pthrp gene is more complex in tetrapods compared with elephant shark. The three elephant shark genes showed distinct patterns of expression, with Pth2 being expressed only in the brain and spleen. This contrasts with localization of the corresponding proteins, which showed considerable overlap in their distribution. There were conserved sites of localization for Pthrp between elephant shark and mammals, including tissues such as kidney, skin, skeletal and cardiac muscle, pancreas, and cartilage. The elephant shark Pth1(1-34) and Pthrp(1-34) peptides were able to stimulate cAMP accumulation in mammalian UMR106.01 cells. However, Pth2(1-34) peptide did not show such PTH-like biologic activity. The presence of Pth and Pthrp genes in the elephant shark indicates that these genes played fundamental roles before their recruitment to bone development in bony jawed vertebrates. ß

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Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception

Cited by 71 publications

References 44 publications

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

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