Calcitonin Gene-Related Peptide
Calcitonin Gene-Related Peptide (CGRP)
CGRP is a potent vasodilator neuropeptide that plays crucial roles in pediatric physiology and pathology. It belongs to the calcitonin family of peptides and exists in two forms: α-CGRP and β-CGRP.
Key Points:
- 37-amino acid neuropeptide
- Primary neurotransmitter in sensory neurons
- Crucial role in migraine pathophysiology
- Important in cardiovascular regulation
- Involved in neurogenic inflammation
Structure and Forms
α-CGRP:
- Expressed primarily in central and peripheral nervous systems
- Alternative splicing of calcitonin gene
- Contains disulfide bridge between positions 2 and 7
- C-terminal amidation essential for biological activity
β-CGRP:
- Differs by three amino acids from α-CGRP
- Encoded by separate gene
- Predominantly expressed in enteric nervous system
- Similar biological activity to α-CGRP
Mechanism of Action
Receptor Interaction:
- Binds to CGRP receptor complex (CLR/RAMP1)
- Activates adenylate cyclase
- Increases intracellular cAMP
- Triggers multiple signaling cascades
Physiological Effects:
- Potent vasodilation
- Neurogenic inflammation
- Pain transmission
- Mast cell degranulation
- Regulation of body temperature
Clinical Applications
Therapeutic Uses:
- Migraine treatment and prevention
- Pulmonary hypertension management
- Pain management
- Cardiovascular disorders
Clinical Considerations:
- Short half-life (≈ 7-10 minutes)
- Requires parenteral administration
- Monitoring for cardiovascular effects
- Cost considerations in therapy
Pediatric Considerations
Age-Specific Concerns:
- Developmental expression patterns
- Age-related receptor sensitivity
- Dose adjustments necessary
- Safety profile in pediatric population
Special Populations:
- Neonatal considerations
- Adolescent migraine management
- Chronic pain conditions
- Cardiovascular disorders in children
