ArticleBritish journal of pharmacology2000
CGRP(2) receptor in the internal anal sphincter of the rat: implications for CGRP receptor classification.
Article in British journal of pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway.Journal of clinical and translational hepatology · 2024Article
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- The effect of topical anal captopril on resting anal pressure in healthy volunteers: the first human pilot study.Techniques in coloproctology · 2014Article
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2 authors at 1 institution in 1 country.
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Abstract
The CGRP receptor mediating relaxation of the rat internal anal sphincter (IAS) has been characterized using CGRP analogues, homologues, the antagonist CGRP(8 - 37) and its analogues. In isolated IAS strips, the spontaneously developed tone was concentration-dependently relaxed by halpha CGRP, hbeta CGRP and rat beta CGRP (pEC(50) 8.1+/-0.2, 8.3+/-0.1 and 8.4+/-0.2, respectively; 100% maximum response). Vasoactive intestinal polypeptide (VIP) was around 7 fold more potent than halpha CGRP (pEC(50) 9.0+/-0.1; 100% maximum relaxation). [Cys(ACM(2.7))] halpha CGRP and salmon calcitonin were inactive (up to 10(-5) M). Halpha CGRP(8 - 37) (10(-5) M) antagonized responses to halpha CGRP (apparent pK(B) 5.7+/-0.3) and rat beta CGRP (apparent pK(B) 5.8+/-0.2), but not to VIP. Hbeta CGRP(8 - 37) (10(-5) M) was an antagonist against halpha CGRP (apparent pK(B) 6.1+/-0.1). Halpha CGRP(8 - 37) analogues (10(-5) M), with substitutions at the N-terminus by either glycine(8) or des-NH(2) valine(8) or proline(8), antagonized halpha CGRP responses with similar affinities (apparent pK(B) 5.8+/-0.1, 5.8+/-0.1 and 5.5+/-0.1, respectively). Peptidase inhibitors (amastatin, bestatin, captopril, phosphoramidon and thiorphan, 10(-6) M each) did not increase the agonist potency of either halpha CGRP or [Cys(ACM(2,7))] halpha CGRP, or the antagonist affinity of halpha CGRP(8 - 37) against halpha CGRP or rat beta CGRP. These data demonstrate for the first time a CGRP receptor in the rat IAS for which halpha CGRP (8 - 37) and its analogues have an affinity that is consistent with a CGRP(2) receptor. However, there is a marked species difference as the antagonist has a 100 fold lower affinity in the rat than in the same tissue of the opossum (Chakder & Rattan, 1991).
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