Figure 8

Schematic representation of mechanisms involved in the induction of hyperresponsiveness in Human ASM. Cytokines and salmeterol up-regulate mRNA expression of the relevant GPCR leading to increased IP₃ production in response to specific contractile agents (as demonstrated in the current manuscript). In addition, cytokines can up-regulate CD38 leading to subsequent increased cADPR production [9]. Second messengers IP₃ and cADPR activate the Ryanodine and IP₃ receptor respectively leading to elevated calcium release from intracellular stores and downstream contractile responses.