In vitro autoradiographic localization of the calcitonin receptor isoforms, C1a and C1b, in rat brain

Hilton, Joanne M.; Chai, Siew Yeen; Sexton, Patrick M.

doi:10.1016/0306-4522(95)00322-a

Cited by 55 publications

(30 citation statements)

References 29 publications

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“…Given that the AP seems to be the primary brain target for amylin action (44), we propose that the ERK cascade may be triggered by direct activation of the amylin-receptor in the AP, which consists of a heterodimer of CTR1(a) (7,24) as a core receptor and a RAMP (15,39), probably RAMP3 (7). This notion is supported by our observation that some AP neurons in which amylin-induced pERK also showed CTR expression.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

Potes

Boyle

Wookey

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Potes CS, Boyle CN, Wookey PJ, Riediger T, Lutz TA. Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect. Am J Physiol Regul Integr Comp Physiol 302: R340 -R351, 2012. First published November 30, 2011 doi:10.1152/ajpregu.00380.2011.-Peripheral amylin inhibits eating via the area postrema (AP). Because amylin activates the extracellular-signal regulated kinase 1/2 (ERK) pathway in some tissues, and because ERK1/2 phosphorylation (pERK) leads to acute neuronal responses, we postulated that it may be involved in amylin's eating inhibitory effect. Amylin-induced ERK phosphorylation (pERK) was investigated by immunohistochemistry in brain sections containing the AP. pERK-positive AP neurons were double-stained for the calcitonin 1a/b receptor, which is part of the functional amylin-receptor. AP sections were also phenotyped using dopamine-␤-hydroxylase (DBH) as a marker of noradrenergic neurons. The effect of fourth ventricular administration of the ERK cascade blocker U0126 on amylin's eating inhibitory action was tested in feeding trials. The number of pERK-positive neurons in the AP was highest ϳ10 -15 min after amylin treatment; the effect appeared to be dosedependent (5-20 g/kg amylin). A portion of pERK-positive neurons in the AP carried the amylin-receptor and 22% of the pERK-positive neurons were noradrenergic. Pretreatment of rats with U0126 decreased the number of pERK-positive neurons in the AP after amylin injection. U0126 also attenuated the ability of amylin to reduce eating, at least when the animals had been fasted 24 h prior to the feeding trial. Overall, our results suggest that amylin directly stimulates pERK in AP neurons in a time-and dose-dependent manner. Part of the AP neurons displaying pERK were noradrenergic. At least under fasting conditions, pERK was shown to be a necessary part in the signaling cascade mediating amylin's anorectic effect.ERK; MAPK; area postrema; amylin receptor; U0126 THE HOMEOSTATIC SYSTEM CONTROLLING food intake and body weight relies to a large extent on peripheral satiation signals.One of these signals is amylin, a peptide cosecreted with insulin by pancreatic ␤-cells in response to nutrient ingestion (12, 41). At near-physiological plasma concentrations, amylin effectively decreases food intake in rats, and is considered a physiological satiation signal (4, 27). The amylin analog pramlintide causes weight loss in obese humans that is accompanied by sustained reductions in 24-h food intake, portion sizes, fast food intake, and binge eating tendencies (5, 57).Pharmacological and lesioning studies implicate the area postrema (AP) as the primary site of amylin's anorectic action (29,30,35), and an excitatory action of amylin on AP neurons has been confirmed by electrophysiological studies (49). Immunohistochemical studies using the immediate early gene product c-Fos as a marker of neuronal activation showed that peripheral amylin activates the AP, and subsequently the nucleus of the solitary tract (NTS),...

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Section: Discussionmentioning

confidence: 99%

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

Potes

Boyle

Wookey

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The CT receptor is also expressed in the CNS at a high level (36) in addition to the peripheral system. Although CT receptor in the CNS has been recognized to be involved in the regulation of appetite (37), gastric acid secretion (38), and analgesic effect (39), endogenous ligands for the CT receptor in the brain remain unidentified.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Katafuchi

Kikumoto

Hamano

et al. 2003

Journal of Biological Chemistry

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We isolated a novel biologically active peptide, designated calcitonin receptor-stimulating peptide (CRSP), from the acid extract of the porcine brain by monitoring cAMP production in the porcine kidney cell line LLC-PK 1 . Determination of the amino acid sequence and cDNA analysis encoding a CRSP precursor showed that this peptide has ϳ60% identity in the amino acid sequence with human calcitonin gene-related peptide type-␣ (␣CGRP), type-␤ (␤CGRP), and porcine CGRP. Northern blot analysis and radioimmunoassay demonstrated that CRSP is expressed mainly in the thyroid gland and the central nervous system, in which the calcitonin receptor was abundantly expressed. Synthetic CRSP elicited a potent stimulatory effect on the cAMP production in LLC-PK 1 cells. Although it shows significant sequence similarity with CGRPs, this peptide did not elicit cAMP elevation in cells that endogenously expressed a CGRP receptor or an adrenomedullin receptor or were transfected with either of these recombinant receptors. Administration of CRSP into anesthetized rats did not alter the blood pressure but induced a transient decrease in the plasma calcium concentration. In fact, this peptide potently increased the intracellular cAMP concentration in COS-7 cells that expressed the recombinant calcitonin receptor. These unique properties indicate that CRSP is not a porcine counterpart of ␤CGRP and probably elicits its biological effects via the calcitonin receptor.Isolation and sequence determination of new biologically active peptides have greatly advanced our understanding of the communication between cells and tissues. Various biologically active peptides, such as natriuretic peptides (1-3) and neuromedins (4), were isolated by monitoring smooth muscle contraction and relaxation. This strategy was useful, but relatively large amounts of tissue extracts were required to monitor the biological activities. Another strategy involving the measurement of intracellular second messenger levels has often been adopted in recent purification studies, and two methods have been successful to date. The first method is to monitor the second messenger levels in intact cultured cells obtained from a particular organ. Pituitary adenylate cyclase-activating peptide and adrenomedullin (AM) 1 were identified by monitoring the adenylyl cyclase activity in the anterior pituitary cells (5) and platelets (6), respectively. The second method is to monitor the second messenger levels in cells expressing a particular orphan receptor. Orexins and ghrelin were purified by monitoring a transient intracellular calcium elevation in HEK293 cells expressing OX 1 R or OX 2 R receptor (7) and growth hormone secretagogue receptor (8), respectively.

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“…Amylin binding has been reported in each of these brain areas, accompanied by calcitonin receptor protein and/or mRNA (Olgiati et al, 1983;Sexton et al, 1994a,b;Christopoulos et al, 1995;Hilton et al, 1995;Skofitsch et al, 1995;Nakamoto et al, 2000;Ueda et al, 2001;Stachniak and Krukoff, 2003;Barth et al, 2004;Becskei et al, 2004;Eftekhari and Edvinsson, 2011). The presence of RAMPs and thus functional amylin receptor subtypes is subject to the same caveats described above.…”

Section: E Expression and Physiologic Relevance Of Amylin Receptor Smentioning

confidence: 95%

Amylin: Pharmacology, Physiology, and Clinical Potential

Hay¹,

Chen²,

Lutz³

et al. 2015

Pharmacol Rev

289

297

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In vitro autoradiographic localization of the calcitonin receptor isoforms, C1a and C1b, in rat brain

Cited by 55 publications

References 29 publications

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

Calcitonin Receptor-stimulating Peptide, a New Member of the Calcitonin Gene-related Peptide Family

Amylin: Pharmacology, Physiology, and Clinical Potential

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