Localization of salmon calcitonin binding sites in rat brain by autoradiography

Henke, H.; Tobler, Paul H.; Fischer, Jan A.

doi:10.1016/0006-8993(83)90587-5

Cited by 86 publications

(17 citation statements)

References 22 publications

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“…Furthermore, it was suggested that CGRP might be an endogenous ligand for calcitonin receptors in the central nervous system and concluded that calcitonin and CGRP may interact on the same receptor site. A detailed comparison of previously published autoradiographic studies of calcitonin-binding sites [7,20] could not be made. However, similarities of localization of binding sites in large areas could be seen.…”

Section: Discussionmentioning

confidence: 99%

Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system

Skofitsch¹,

Jacobowitz²

1985

Peptides

144

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SKOFITSCH, G. AND D. M. JACOBOWITZ. Autoradiographic distribution of v'-:'l calcitonin gene-related peptide binding sites in the rat central nervous system. PEPTIDES 6(5) [975][976][977][978][979][980][981][982][983][984][985][986] 1985.--Using autoradiographic method and "-':'I-Tyr ° rat CGRP as a ligand, receptor binding sites were demonstrated in the rat central nervous system. Saturation studies and Scatchard analysis of CGRP-binding to slide mounted tissue sections containing primarily cerebellum showed a single class of receptors with a dissociation constant of 0.96 nM and a Bm,~x of 76.4 fmol/mg protein, v-'~I-Tyr ° rat CGRP binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the telencephaIon (medial prefrontal, insular and outer layers of the temporal cortex, nucleus accumbens, fundus striatum, central and inferior lateral amygdaloid nuclei, most caudal caudate putamen, organum vasculosum laminae terminalis, subfornical organ), the diencephalon (anterior hypothalamic, suprachiasmatic, arcuate, paraventricular, dorsomedial, periventricular, reuniens, rhomboid, lateral thalamic pretectalis and habenula nuclei, zona incerta), in the mesencephalon (superficial layers of the superior colliculus, central nucleus of the geniculate body, inferior colliculus, nucleus of the fifth nerve, locus coeruleus, nucleus of the mesencephalic tract, the dorsal tegmental nucleus, superior olive), in the molecular layer of the cerebellum, in the medulla oblongata (inferior olive, nucleus tractus solitarii, nucleus commissuralis, nuclei of the tenth and twelfth nerves, the prepositus hypoglossal and the gracilis nuclei, dorsomedial part of the spinal trigeminal tract), in the dorsal gray matter of the spinal cord (laminae I-VI) and the confines of the central canal. Moderate receptor densities were found in the septal area, the "head" of the anterior caudate nucleus, medial amygdaloid and bed nucleus of the stria terminalis, the pyramidal layers of the hippocampus and dentate gyri, medial preoptic area, ventromedial nucleus, lateral hypothalamic and ventrolateral thalamic area, central gray, reticular part of the substantia nigra, parvoceUular reticular nucleus, Purkinje cell layer of the cerebellum, nucleus of the spinal trigeminal tract and gracile fasciculus of the spinal cord. The discrete distribution of CGRP-like binding sites in a variety of sensory systems of the brain and spinal cord as well as in thalamic and hypothalamic areas suggests a widespread involvement of CGRP in a variety of brain functions.Calcitonin gene-related peptide CGRP Autoradiography CNS ALTERNATE processing of the rat and human calcitonin genes resulted in a novel peptide, the calcitonin gene-related peptide (CGRP) [1,26,27,33]. This peptide was recently isolated and characterized [18,19]. The 37 amino acid human CGRP was found to differ from rat CGRP in four amino acids. CGRP-Iike immunoreactivity was shown to be widely distributed in the central and peripheral nervous system of man, rat and o...

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Section: Discussionmentioning

confidence: 99%

Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system

Skofitsch¹,

Jacobowitz²

1985

Peptides

144

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“…Further suggesting a difference between CGRP and CT was the observation that the regional distribution in the human and rat nervous system of 125I-CGRP binding sites differed from that of salmon 1251-CT (10,(17)(18)(19) (20,21). Evidence for physiological roles of CORP in the central nervous system has been obtained recently by intracerebral administration of synthetic CGRP resulting in an increased noradrenergic sympathetic outflow and a concomitant rise in blood pressure (22) and in inhibition of gastric secretion (23).…”

Section: Discussionmentioning

confidence: 99%

Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary.

Tschopp¹,

Henke²,

Petermann³

et al. 1985

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

211

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Binding sites for synthetic human 1251-labeled calcitonin gene-related peptide (125I-CGRP) have been demonstrated in membranes of the human nervous system. Binding was high in the cerebellar cortex (1.35 ± 0.27 fmol/mg of tissue; mean ± SEM), spinal cord (1.06 ± 0.27 to 1.27 ± 0.23 fmol/mg), and nucleus dentatus (1.02 ± 0.15 fmol/mg), intermediate in the inferior colliculus (0.80 ± 0.14 fmol/mg) and substantia nigra (0.75 ± 0.14 fmol/mg), low in the neocortex, globus pallidus, nucleus caudatus, hippocampus, amygdala, superior colliculus, thalamus, and hypothalamus (0.15-0.32 fmol/mg), and negligible in spinal and sympathetic ganglia and pituitary (<0.04 fmol/mg). Autoradiography showed distinct 1251-CGRP binding over the molecular and Purkinje cell layers of the cerebellar cortex and over the substantia gelatinosa posterior of the spinal cord. The highest levels of CGRP-like components were recognized in the dorsal part of the spinal cord and the pituitary gland. In the ventral part of the spinal cord as well as in the pituitary and thyroid glands, CGRP values were higher when measured by radioreceptorassay as compared to RIA, indicating that at least two CGRP-like components are present. The predominant CGRPlike peak on HPLC had the retention time of synthetic human CGRP. Immunohistochemistry revealed the presence of a dense plexus of CGRP immunoreactive nerve fibers in the dorsal horn of the spinal cord.The existence of rat and human calcitonin gene-related peptide (CGRP) has been predicted by analysis of the nucleotide sequence of the calcitonin gene (1, 2). CGRP is a unique 37 amino acid peptide that shares greater structural homology with salmon calcitonin-(1-32) than with rat and human calcitonin-(1-32) (1-3). Expression of CGRP was shown immunohistochemically and by specific RIA in combination with gelpermeation chromatography and HPLC in the nervous system and in the pituitary and thyroid glands (4-6). The amino acid sequence was derived from human medullary carcinoma of the thyroid (7).Here we report distinct regional distribution of CGRP and calcitonin (CT) binding sites in the human central nervous system. The presence of endogenous CGRP-like components in the nervous system, pituitary, and thyroid was revealed by a radioreceptorassay (RRA) using human cerebellar membranes, by RIA, and by immunohistochemistry. MATERIALS AND METHODSTissues and Peptides. Tissue obtained at autopsy within 20 hr postmortem was frozen on dry ice and stored at -80°C for a maximum of 3 wk. Patients with malignant tumors, chronic renal insufficiency, or metabolic bone disease were excluded from the study.Synthetic salmon CT-( Receptor Binding Studies. Membranes were prepared and incubated as described (8, 9) with 17,000 dpm (1 dpm = 16.7 mBq) of human 125I-labeled CGRP (125I-CGRP) Ci/mmol) or salmon 125I-labeled CT (125I-CT) Ci/mmol). Specific binding was defined as total binding minus binding in the presence of 0.7 ,uM unlabeled human CGRP or salmon CT, respectively. A RRA for CGRP was developed using membranes fro...

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“…and same has been observed in experimental studies carried out by injecting Salmon calcitonin directly into the lateral cerebral ventriculi in rats and was suggested to be because of correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose-effect relationship. 19 In our study with the use of 100IU salmon calcitonin the duration of analgesia following subarachnoid block was 230±92.39 minutes which is slightly less though nearly similar to that observed by Moraby et al but, the standard deviation of 2.39min suggested that the postoperative analgesic effects were quite variable and was found to quite long lasting in some patients. 11 Miralles et al in their group of patients have used 100IU.…”

Section: Discussionmentioning

confidence: 62%

“…It's presence in nervous tissue suggest that it may have range of action that exceeds its role in calcium and phosphorus metabolism. [16][17][18][19] A nonopiate analgesic pathway has been suggested as calcitonin induced analgesic effect is not modified by opioids antagonists. 20 Other pathways suggested so far increases in the plasma beta-endorphin levels at the hypothalamus and/or the pituitary level, involvement of the serotonergic system.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of two different doses of intrathecal calcitonin, a randomized controlled study

2018

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Background: Adjuvants play an important role in enhancing the quality of anesthesia and also in reducing the requirement of primary anesthetic and its related adverse events. Calcitonin is one such adjuvant. But there is still uncertainty regarding the appropriate dose of calcitonin to achieve maximum analgesic efficacy and safety. The current study is conducted to add to the existing evidence on the subject and was aimed to compare the efficacy and safety of two different doses of calcitonin as an adjuvant in patients undergoing spinal anesthesia.Methods: A prospective randomized controlled double-blind trial was conducted in the Department of Anesthesiology and Intensive Care, Sir Sunderlal Hospital, Banaras Hindu University from May 2006 to May 2007. A total of 80 participants aged between 18 to 60 years, with ASA I and II physical status, undergoing infra-umbilical surgeries were randomly allocated to one of the 4 intervention groups. All the 4 intervention groups received 0.5% bupivacaine (H) 3ml as a primary anesthetic agent. Group I and III received 50 IU and 100 IU salmon calcitonin as an adjuvant. Group II received placebo and group IV (control) received no adjuvant. Pinprick test, Bromage scale and 10-point Visual analog scale (VAS) were used to measure the efficacy.Results: All the study groups were comparable with respect to all baseline variables. The time interval to the first dose of analgesia was longest in 100 I.U. calcitonin group, followed by 50 I.U. calcitonin group, placebo control group. The mean duration of analgesia (in minutes) among group I (100I.U. calcitonin) was 230.00±92.39, 159.25±21.59 among group II (Placebo), 161.50±31.20 among group III (50 I.U. calcitonin) and 142.75±20.22 among group IV. Considering group IV (control group) as base line. The differences of duration of analgesia (in minutes) in group I, group II and group III with baseline value (group IV) were statistically significant (P value <0.05). Even though the proportion of subjects developing adverse events was slightly higher in 100 I.U calcitonin groups compared to other groups, they were minor adverse events and were managed appropriately. There were no significant differences across the study groups in terms of hemodynamic stability.Conclusions: Salmon calcitonin as adjuvant increases the duration of postoperative analgesia. Even though the there slightly higher incidence of adverse events with 100 I.U calcitonin they are minor and the risk-benefit ratio favors calcitonin use. To make a categorical recommendation on the appropriate dose, there is further need for large-scale studies and pooled analysis.

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Localization of salmon calcitonin binding sites in rat brain by autoradiography

Cited by 86 publications

References 22 publications

Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system

Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system

Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary.

Efficacy and safety of two different doses of intrathecal calcitonin, a randomized controlled study

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