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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Antagonism of calcitonin gene-related peptide (CGRP) by human CGRP-(8-37): role of CGRP in internal anal sphincter relaxation.

We performed functional studies on the opossum internal anal sphincter (IAS) smooth muscle strips and receptor binding studies in the IAS smooth muscle membranes to examine the influence of: human calcitonin gene-related peptide (CGRP)-(8-37) on the fall in IAS tension caused by human CGRP I and CGRP II and on [125I]human CGRP I binding on the IAS smooth muscle membranes. We also compared the ability of [Tyr0]-rat CGRP 28-37 to displace the radioligand from the IAS membranes to that of human CGRP-(8-37). Human CGRP-(8-37) caused significant and dose-dependent right-ward shifts of the dose-response curves of both CGRP I and CGRP II on the IAS smooth muscle. The specific binding of [125I]human CGRP I to IAS smooth muscle membranes was time- and temperature-dependent. CGRP antagonists human CGRP-(8-37) and [Tyr0]-rat CGRP 28-37 and CGRP I and CGRP II caused dose-dependent displacement of the radioligand. Vasoactive intestinal polypeptide and calcitonin on the other hand had no significant effect on the radioligand binding. Tachyphylaxis and cross tachyphylaxis to the effects of CGRP I and CGRP II were observed. The CGRP antagonists and CGRP I and CGRP II tachyphylaxis failed to modify the fall in the IAS tension in response to neural stimulation by electrical field stimulation. From these studies we conclude: human CGRP-(8-37) and [Tyr0]-rat CGRP 28-37 may serve as potential antagonists of CGRP action; human CGRP I and CGRP II may act on the same receptor on the IAS smooth muscle; and CGRP may not play a significant role in the IAS relaxation in response to electrical field stimulation.[1]


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