Structure-Activity Relationship of Calcitonin Gene Related Peptide

Morita, Keiko; Kato, Ikuo; Uzawa, Toyonobu; Hori, Masayuki; Noda, Toshiharu

doi:10.1055/s-2007-1009315

Cited by 13 publications

(11 citation statements)

References 12 publications

(12 reference statements)

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“…Similar difference in hypocalcemic activity between cCGRP and hCGRP has been reported in rats in vivo (13). Furthermore, in cCGRP, the replacement of aspartic acid at position 14 by glycine, which is the corresponding amino acid for hCGRP, has been shown to reduce the hypocalcemic activity, while the replacement of glycine at position 14 of hCGRP with aspartic acid increased the activity (13). Therefore, aspartic acid at position 14 may also be im portant for the biological activity of this peptide.…”

Section: Discussionsupporting

confidence: 83%

“…Because the vasodilator activities of cCGRP and rCGRP are greater than that of hCGRP, the 3rd amino acid residue (asparagine in the human peptide and aspartic acid in the chicken and rat peptides) may play an important role in vasodilator activity. Similar difference in hypocalcemic activity between cCGRP and hCGRP has been reported in rats in vivo (13). Furthermore, in cCGRP, the replacement of aspartic acid at position 14 by glycine, which is the corresponding amino acid for hCGRP, has been shown to reduce the hypocalcemic activity, while the replacement of glycine at position 14 of hCGRP with aspartic acid increased the activity (13).…”

Section: Discussionsupporting

confidence: 69%

“…On the contrary, (des-1-Ala)-a-deamino cCGRP, which conserves the di sulfide bridge but has no a-amino group in its N-terminal, caused a potent and long-lasting vasodilator response, similar to cCGRP and rCGRP. The removal of the a amino group in the N-terminal has been shown to confer resistance against aminopeptidase (13). Therefore, (des 1-Ala)-a-deamino cCGRP may have induced stronger vasodilation by resisting degradation by aminopeptidase.…”

Section: Discussionmentioning

confidence: 99%

“…Because CGRP has a potent vasodilator effect (5) and acts as a vasodilator neurotransmitter (6), this pep tide is considered to be involved in the control of the tone of resistance blood vessels (6)(7)(8)(9). In addition, CGRP has a variety of biological actions such as hypotension (10), cardiac acceleration (11,12), increase of regional blood flow (10,12), regulation of calcium metabolism (13) and insulin secretion (14). Two forms of CGRP, a and j3 CGRP, have been isolated from human and rat tissue (15).…”

mentioning

confidence: 99%

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Structure-Activity Study of Chicken Calcitonin Gene-Related Peptide (CGRP) on Vasorelaxation in Rat Mesenteric Resistance Vessels.

et al. 1994

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ABSTRACT-Structure-activity relationship of the chicken calcitonin gene-related peptide (cCGRP) was investigated and compared with human-a-CGRP (hCGRP) and rat CGRP (rCGRP) in the perfused mesenteric vascular beds of rats. In precontracted mesenteric vascular beds, cCGRP, hCGRP and rCGRP produced a concentration-dependent vasodilation. The vasodilator activities of cCGRP and rCGRP were equipotent and more potent than that of hCGRP. (Ala2,')cCGRP and (Des-l-Ala)-a-deamino cCGRP were 100 and 10-fold less potent than cCGRP, respectively. However, cCGRP curves of rCGRP to the right, but both peptides did not affect the maximum response and vasodilator responses to isoproterenol, these peptides being equipotent an tagonists (pA2 values: 7.6 and 7.4). In rat brain membrane preparations, cCGRP and its fragments and analogues, except for cCGRP , competed for specific binding sites with [125I]-hCGRP. These results suggest that cCGRP has a potent vasodilator activity for which the disulfide bridge at position 2 and 7 of cCGRP is an important site and that position 37 is necessary for the binding of the peptide to the receptor. Also, cCGRP [8 37] is a competitive CGRP-receptor antagonist.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Structure-Activity Study of Chicken Calcitonin Gene-Related Peptide (CGRP) on Vasorelaxation in Rat Mesenteric Resistance Vessels.

et al. 1994

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“…We used Des-l-Ala, des-a-amino chicken CGRP (Asahi Chemical Industry, Tokyo, Japan). This CGRP has been identified as having a 4-amino-acid difference from human CGRP (c~) [15].…”

Section: Experimental Protocolmentioning

confidence: 99%

Halothane anesthesia suppresses reflex tachycardia caused by calcitonin gene-related peptide in dogs

et al. 1996

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Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg(-1) of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg(-1)) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg(-1) CGRP but remained unchanged at the 40 μg·kg(-1) infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg(-1). In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg(-1) produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia.

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Structure-activity relationships in calcitonin gene-related peptide: Cyclic AMP response in a preosteoblast cell line (ks-4)

Thiébaud

Akatsu

Yamashita

et al. 1991

Journal of Bone and Mineral Research

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Synthetic analogs of chicken and human CGRP were used to define structure-function relationships in a murine osteoblast precursor cell line, KS-4, that exhibits a substantial cyclic AMP response to CGRP but no response to calcitonin. Human CGRP had 40% of the activity of chicken CGRP, but [Asp-14]-human CGRP was equipotent with chicken CGRP. Similar observations were made previously for calcium- and phosphate-lowering effects. Des-1-Ala,deamino CGRP compounds of both human and chicken origin were three-fold more potent than the respective native CGRPs. The [4-F-Phe)-37]-chicken CGRP analog had a four-fold enhanced activity. In all of the 13 analogs either truncated amino-terminally or missing the (2-7)-disulfide bridge, biologic activity was greatly reduced (0.1% of chicken CGRP), as it was in chicken CGRP-(1-36)-OH, which lacks the C-terminal amino acid. The same analog has been shown to retain a hypocalcemic effect, which is most likely mediated through calcitonin receptors. In confirmation of their antagonistic effect reported in liver, analogs that lack the N-terminal ring structure exhibited significant antagonistic activity. The data illustrate the specificity of CGRP receptors in promoting cyclic AMP formation in osteoblast-like cells. Such CGRP analogs will be useful in investigating structure-function relationships of CGRP.

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Structure-Activity Relationship of Calcitonin Gene Related Peptide

Cited by 13 publications

References 12 publications

Structure-Activity Study of Chicken Calcitonin Gene-Related Peptide (CGRP) on Vasorelaxation in Rat Mesenteric Resistance Vessels.

Structure-Activity Study of Chicken Calcitonin Gene-Related Peptide (CGRP) on Vasorelaxation in Rat Mesenteric Resistance Vessels.

Halothane anesthesia suppresses reflex tachycardia caused by calcitonin gene-related peptide in dogs

Structure-activity relationships in calcitonin gene-related peptide: Cyclic AMP response in a preosteoblast cell line (ks-4)

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