Time-dependent synergistic interactions between the vasodilator neuropeptide, calcitonin gene-related peptide (CGRP) and mediators of inflammation

Abstract

1. The action of the long lasting neuropeptide vasodilator, calcitonin gene-related peptide (CGRP), in potentiating oedema formation and neutrophil accumulation was investigated in the dorsal skin of the rabbit, in vivo. Combinations of agents under test were administered by intradermal (i.d.) injection. Oedema formation and neutrophil accumulation were then measured by quantitative radiolabel techniques. 2. CGRP (1 x 10(-11) mol per site) potentiated neutrophil accumulation induced by zymosan activated plasma, (used as a source of C5a des Arg), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). In contrast CGRP did not induce neutrophil accumulation when injected alone. 3. Oedema formation induced by a series of chemically distinct mediators of increased microvascular permeability; bradykinin, platelet activating factor (PAF), FMLP and zymosan-activated plasma; measured 0-30 min after i.d. injection was potentiated by CGRP (1 x 10(-11) mol per site). 4. Oedema formation induced by zymosan activated plasma and FMLP but not bradykinin and PAF, was also significantly potentiated by CGRP when oedema was measured 30-60 min after i.d. injection. The potentiation of oedema induced by zymosan activated plasma measured 30-60 min after i.d. injection was not observed in the presence of the shorter acting prostanoid vasodilator prostacyclin (PGI2, 3 x 10(-10) mol per site). 5. These results suggest that CGRP, as a consequence of its sustained vasodilator activity could have prolonged potentiating effects on neutrophil accumulation and oedema formation in inflammatory conditions.