Differential antagonism of amylin's metabolic and vascular actions with amylin receptor antagonists

1995 ◽  
Vol 73 (7) ◽  
pp. 1025-1029 ◽  
Author(s):  
K. Beaumont ◽  
C. X. Moore ◽  
R. A. Pittner ◽  
K. S. Prickett ◽  
L. S. L. Gaeta ◽  
...  

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.

2004 ◽  
Vol 362 (2) ◽  
pp. 146-149 ◽  
Author(s):  
Ning Li ◽  
Chun-Yan Fang ◽  
Zun-Zhe Wang ◽  
Yü-Liang Wang ◽  
Feng-Bin Wang ◽  
...  

1990 ◽  
Vol 258 (2) ◽  
pp. L81-L88 ◽  
Author(s):  
J. N. Baraniuk ◽  
J. D. Lundgren ◽  
J. Goff ◽  
J. Mullol ◽  
S. Castellino ◽  
...  

To explore the potential range of functions for calcitonin gene-related peptide (CGRP) in human mucosa, we quantified human inferior turbinate nasal mucosal CGRP content by radioimmunoassay, localized CGRP-immunoreactivity by immunohistochemistry, detected 125I-CGRP binding sites by autoradiography, and tested the ability of CGRP to induce submucosal gland secretion in short-term explant culture of human nasal mucosa. Nasal mucosa contained 0.45-0.54 pmol CGRP/g wet wt (n = 18). Immunoreactive CGRP was found in nerve fibers that densely innervated the walls of small muscular arteries arterioles. Venules and venous sinusoids were innervated by individual CGRP staining fibers. Occasional CGRP-containing nerve fibers were also noted adjacent to submucosal gland acini, near the epithelial basement membrane, and between epithelial cells. Specific 125I-CGRP binding sites were concentrated on small muscular arteries and arterioles. CGRP (4 microM) did not stimulate glycoconjugate or lactoferrin release from mucosal explants. These results indicate that in the human nasal mucosa, CGRP is present in nerve fibers, which most likely represent nociceptive sensorimotor nerves that innervate vascular structures (muscular arteries, arterioles, veins and venous sinusoids). It is likely that CGRP release from sensory neurons may play a role in the regulation of vasomotor responses, but no evidence for a role of CGRP in glandular secretion was found.


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