生物活性

• 描述Rat CGRP-(8-37) TFA salt, a cholestanol-conjugated antagonist, accumulated in CLR(calcitonin receptor-like receptor)-containing endosomes and selectively inhibited CLR signaling in endosomes. CGRP8-37-cholestanol, but not unconjugated CGRP8-37, prevented sustained neuronal excitation. When injected intrathecally to mice, CGRP8-37-cholestanol inhibited nociceptive responses to intraplantar injection of capsaicin, formalin, or complete Freund's adjuvant more effectively than unconjugated CGRP8-37^[3]. CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP-(8-37) is effective in alleviating mechanical and thermal allodynia in a dose-dependent manner. The 50 nM dose is most efficacious for both forelimb and hindlimb responses. The period of efficacy is 10 min to onset for a duration of 20 min^[4]. Intrathecal administration of 5 nmol or 10 nmol of CGRP-(8-37), but not 1 nmol, induces a significant increase in hindpaw withdrawal latency. Intrathecal administration of CGRP-(8-37) not only reverses the SP-induced decrease in latency to both withdrawal responses but also mediates a significant increase in response latency compared to basal levels^[5].