The role of calcitonin gene-related peptide in the regulation of anion secretion by the rat and human epididymis

1992 ◽  
Vol 133 (2) ◽  
pp. 259-NP ◽  
Author(s):  
A. Y. H. Leung ◽  
P. Y. Leung ◽  
S. B. Cheng-Chew ◽  
P. Y. D. Wong
Keyword(s):  
Short Circuit ◽  
Calcitonin Gene Related Peptide ◽  
Bathing Solution ◽  
Dependent Manner ◽  
Anion Secretion ◽  
Human Epididymis ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

ABSTRACT A study was carried out to investigate the role of the calcitonin gene-related peptide (CGRP) in the regulation of electrolyte transport in the rat and human epididymis. In monolayer cultures derived from the rat cauda epididymal cells, CGRP stimulated the short-circuit current (SCC) in a dose-dependent manner with the EC50 (concentration required to produce 50% of the response) at 15 nmol/l. This effect of CGRP was seen when the peptide was added to the basolateral aspect of the cells; apical addition having negligible effect. The CGRP-induced rise in the SCC was dependent on the presence of chloride in the bathing solution. Calcitonin had no effect on the SCC and did not affect the CGRP-induced rise in the SCC. The effect of CGRP on secretion was inhibited in a competitive fashion by the CGRP receptor antagonist CGRP(8–37). In contrast to bradykinin, angiotensin II and endothelin I, the effect of CGRP was independent of prostaglandin synthesis. Measurement of intracellular adenosine 3′:5′-cyclic monophosphate showed a time- and dose-dependent increase upon stimulation with CGRP. CGRP also stimulated the SCC in monolayers grown from the human epididymis. The current could be inhibited by apical application of the chloride channel blocker, diphenylamine-2-carboxylate. Immunoreactive CGRP was found in the epithelia of rat and human cauda epididymidis. It is suggested that CGRP may regulate the electrolyte and fluid secretion in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa. Journal of Endocrinology (1992) 133, 259–268

Characteristics of relaxation induced by calcitonin gene—related peptide in contracted rabbit basilar artery

1995 ◽  
Vol 82 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Bernhard Sutter ◽  
Satoshi Suzuki ◽  
Neal F. Kassell ◽  
Kevin S. Lee
Keyword(s):  
Basilar Artery ◽  
Contractile Response ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Vascular Response ◽  
Content Type ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent ◽  
Fine Print

✓ Increasing evidence suggests that disturbances in the modulatory influence of the vasoactive peptide, calcitonin gene—related peptide (CGRP), contribute to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, only limited success has been achieved in trials attempting to ameliorate vasospasm by modifying CGRP function. To better understand the potential utility of targeting CGRP-mediated relaxation, it is important both to identify the interactions CGRP may have with other elements of the vasospastic response and to characterize the mechanisms through which CGRP elicits vasodilative effects. The present studies examined the effects of CGRP on vascular responsiveness using tension measurements of ring strips of rabbit basilar artery maintained in vitro. Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to the potent protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDB). This particular contractile response was selected because PKC-mediated vasoconstriction is a critical component of the vasospastic response after SAH. In a posttreatment paradigm, CGRP was also found to reverse established constriction responses to PDB (2 nM) and histamine (3 µM) in a dose-dependent manner. When tested against the maximum effective dose of PDB (30 nM) in the posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation. However, after washing both of these drugs out of the test chamber, a persistent effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated in vessels that had previously been treated with CGRP. These findings indicate that CGRP elicits both immediate and sustained influences on contractile responses mediated by PKC. Finally, two potential mechanisms for the vascular response to CGRP were examined. Adenosine triphosphate (ATP)—sensitive K+ channels do not appear to participate in CGRP-mediated dilation; inhibitors of these channels, glibenclamide and tolbutamide, did not block CGRP-induced relaxation. In contrast, a possible role for the nucleotide cyclic adenosine monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose-dependent elevation of cAMP levels by CGRP. Together these studies indicate that CGRP can modulate the contractile response to PKC activation. These effects are associated with increases in the levels of cAMP, but occur independently of fluxes through ATP-sensitive K+ channels.

scholarly journals Effects of Adrenomedullin, Calcitonin Gene-Related Peptide, and Amylin on Cerebral Circulation in Dogs

1995 ◽  
Vol 15 (5) ◽  
pp. 827-834 ◽  
Author(s):  
Mustafa K. Baskaya ◽  
Yoshio Suzuki ◽  
Masaoki Anzai ◽  
Yukio Seki ◽  
Kiyoshi Saito ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Circulation ◽  
Cerebral Arteries ◽  
Calcitonin Gene Related Peptide ◽  
Bolus Administration ◽  
Dependent Manner ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

The effect of human adrenomedullin on cerebral circulation was investigated in dogs in vivo and in vitro. Bolus administration of adrenomedullin or its homologous peptides, calcitonin gene-related peptide (CGRP) and amylin, into the vertebral artery induced a dose-dependent increase in vertebral blood flow. The potencies of adrenomedullin and CGRP were similar and approximately 100 times more than that of amylin. The effects of adrenomedullin and CGRP were inhibited by CGRP8-37, an antagonist of CGRP. In contrast to substance P, adrenomedullin did not induce an increase in blood flow after prior administration of CGRP. Pretreatment with either NG-nitro-l-arginine methyl ester or indomethacin did not affect the adrenomedullin-induced increase in blood flow. Intracisternal administration of adrenomedullin induced dilation of the basilar and other major cerebral arteries in a dose-dependent manner, accompanied by an increase in the concentration of cyclic AMP in the cerebrospinal fluid. Adrenomedullin also induced relaxation of isolated basilar and middle cerebral arterial rings. These data suggest that adrenomedullin induces vasodilation of cerebral arteries and an increase in vertebral blood by acting at CGRP receptors positively coupled to adenylate cyclase, and that these effects are not dependent on nitric oxide or prostaglandin formation.

Role of calcitonin gene-related peptide in energy metabolism

Endocrine ◽  
2017 ◽  
Vol 58 (1) ◽  
pp. 3-13 ◽  
Author(s):  
William Gustavo Lima ◽  
Gleuber Henrique Marques-Oliveira ◽  
Thaís Marques da Silva ◽  
Valéria Ernestânia Chaves
Keyword(s):  
Energy Metabolism ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Role of calcitonin gene-related peptide in gastric hypersensitivity in rats

2006 ◽  
Vol 14 (25) ◽  
pp. 2484
Author(s):  
Fei-Fei Zhang ◽  
Jian-Zhong Mo ◽  
You-Ling Lv ◽  
Sheng-Liang Chen ◽  
Ming Lv ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors

2021 ◽  
Vol 8 ◽  
Author(s):  
Giuseppe Deganutti ◽  
Silvia Atanasio ◽  
Roxana-Maria Rujan ◽  
Patrick M. Sexton ◽  
Denise Wootten ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Ligand Binding ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Approved Drugs ◽  
G Protein Coupled ◽  
Dynamic Docking ◽  
Receptor Family

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity.

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