Calcitonin gene-related peptide and calcitonin receptors: Effects of cerebral lesions in the rat nucleus accumbens and ventral tegmental area

High affinity amylin binding sites are present in the rat nucleus accumbens. These sites bind [125I]amylin with an affinity of 27 pM and have high affinity for salmon calcitonin (sCT) and moderately high affinity for calcitonin gene related peptide (CGRP). N-terminally truncated peptides were tested for their ability to compete for [125I]amylin binding to these sites and to antagonize the metabolic and vascular actions of amylin. CGRP(8–37), sCT(8–32), and ac-[Asn30,Tyr32]sCT(8–32) (AC187) inhibited [125I]amylin binding to rat nucleus accumbens. Order of potency at inhibiting amylin binding (AC187 > sCT(8–32) > CGRP(8–37)) differed from the order of potency at inhibiting [125I]CGRP binding to SK-N-MC neuroblastoma cells (CGRP(8–37) > AC187 > sCT(8–32)). AC187 was the most potent antagonist of amylin's effects on isolated rat soleus muscle glycogen metabolism, and it was more effective than either sCT(8–32) or CGRP(8–37) at reducing amylin-stimulated hyperlactemia in rats. In contrast, CGRP(8–37) was the most potent peptide at antagonizing amylin-induced hypotension in rats. Amylin's hypotensive actions appear to be mediated by a weak action at CGRP receptors, while its metabolic actions are mediated by receptors with a distinct antagonist profile. AC187 is a potent antagonist of amylin binding sites in nucleus accumbens and of amylin's metabolic actions.Key words: amylin, calcitonin gene related peptide, diabetes, skeletal muscle, peptide receptors.

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Investigation of a novel binding site for the calcitonin gene related peptide (CGRP) family of peptides in rat nucleus accumbens

Regulatory Peptides ◽

10.1016/0167-0115(93)90321-x ◽

1993 ◽

Vol 47 (1) ◽

pp. 111

Author(s):

Philippa Veale ◽

Ranjev Bhogal ◽

David Smith ◽

Stephen Bloom

Keyword(s):

Nucleus Accumbens ◽

Binding Site ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Calcitonin Gene ◽

Rat Nucleus Accumbens

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Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.256.2.e331 ◽

1989 ◽

Vol 256 (2) ◽

pp. E331-E335 ◽

Cited By ~ 21

Author(s):

T. Chiba ◽

A. Yamaguchi ◽

T. Yamatani ◽

A. Nakamura ◽

T. Morishita ◽

...

Keyword(s):

Plasma Membrane ◽

Adenylate Cyclase ◽

Calcitonin Gene Related Peptide ◽

Human Calcitonin ◽

Liver Plasma Membrane ◽

Related Peptide ◽

Calcitonin Gene ◽

Liver Membranes ◽

Calcitonin Receptors ◽

Stimulation Of

From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.

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