Mechanisms of α(1B)-adrenergic receptor signalling

We have used a cloncal isolate of Madin-Darby Canine Kidney cells (MDCK- D₁) to define mechanisms whereby α(1b)-adrenergic receptors regulate second messengers responsible for regulation of functions, such as ion transport, in the portions of the renal tubule from which MDCK cells were derived. Our findings indicate a complex schema whereby these receptors link via one or more heterotrimeric GTP binding proteins to multiple phospholipases including multiple forms of phospholipase C, phospholipase D, and phospholipase A₂ (PLA₂). Activation of PLA₂, in particular cPLA₂, depends upon activation of MAP kinase, in large part secondary to activation of protein kinase C (PKC). By contrast, phospholipase D activation, although highly calcium- dependent, appears independent of the activation of MAP kinase and also appears independent of at least two isoforms of PKC, PKC(α) and PKC(ε). Based on differences between the activation of such phospholipases for other agonists (e.g. bradykinin, ATP) that activate similar pathways, it appears that different types of G protein-coupled receptors regulate similar signalling pathways but achieve this regulation via different mechanisms.