CLINICAL PERSPECTIVES OF CALCITONIN-GENE-RELATED PEPTIDE PHARMACOLOGY

Calcitonin gene related peptide (CGRP), a potent vasoactive and cardio tonic peptide, interacts with specific G-protein-coupled receptors. CG RP is synthesized and released from small, capsaicin-sensitive sensory nerves. This extensive network of sensory nerves, found in virtually all organs, suggest a potential role for CGRP in diverse physiologic a nd pathophysiologic processes. The potent vasodilation elicited by CGR P in the cerebral, coronary, and peripheral vasculature has led to its therapeutic evaluation in the treatment of cerebral vasospasm followi ng subarachnoid hemorrhage, stable angina, and Raynaud's phenomenon. T he potential inotropic action and coronary vasodilation have also led to a potential beneficial effect in congestive heart failure. The enri ched localization of CGRP in trigeminal sensory ganglia may indicate a role in the neurogenic inflammation associated with migraine. Thus, C GRP antagonists may represent a novel therapeutic approach to the trea tment of migraine. In addition, CGRP and amylin (homologous pancreatic peptide) reduce the tissue-glucose response to insulin. It has been s uggested that a CGRP antagonist may therefore improve insulin sensitiv ity in non-insulin-dependent diabetes, NIDDM. This brief review provid es a preliminary exploration of the potential therapeutic opportunitie s surrounding CGRP and CGRP antagonists. Future advances are dependent on a better understanding of the structure and function of CGRP recep tor(s) and the concomitant identification of selective and potent agon ists and antagonists useful for addressing therapeutic hypotheses.