Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP

We have studied the ability of cGMP and cAMP to modulate platelet-derived g rowth factor (PDGF)-stimulated 2-deoxy-D-glucose (deGlc) transport in prima ry cultures of vascular smooth muscle cells (VMSC) from rat aorta. PDGF sti mulated deGlc transport in a time- and concentration-dependent manner. 8-Br omo-cGMP and atrial natriuretic peptide(1-28) [ANP(1-28)] were found to red uce PDGF-stimulated deGlc transport without affecting basal (unstimulated) transport activity. In contrast, 8-bromo-cAMP and dibutyryl-cAMP stimulated basal deGlc transport 2-fold and were without effect on PDGF-stimulated de Glc transport. 8-Bromo-cGMP also inhibited 8-bromo-cAMP-stimulated deGlc tr ansport, The stimulation of deGlc transport by PDGF was sensitive to the mi togen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase (MEK) inhibitor PD98059, and we show that ERK1/2. was activat ed by PDGF. Neither 8-bromo-cGMP nor ANP(1-28) inhibited PDGF-stimulated ER K activation, suggesting that the effects of cGMP and ANP(1-28) were not me diated by inhibition of this kinase, Our data also argue against a role for cGMP-dependent protein kinase in mediating the effects of cGMP or ANP(1-28 ), Collectively, our data suggest that in VSMC: (i) cGMP and cAMP have oppo sing effects on deGlc transport; (ii) PDGF and cAMP have common elements in the pathways by which they activate deGlc transport; and (iii) a common el ement may be the target of the cGMP-mediated inhibition of deGlc transport.