The mesangial cell is a glomerular cell type with smooth muscle-like (contractile) properties. The responses evoked in cultured mesangial cells by catecholamines were examined in the presence or absence of prostaglandin E2 (PGE2) with or without a phosphodiesterase inhibitor. Exposure to 10-4 M norepinephrine, epinephrine, or isoproterenol elevated intracellular cyclic AMP (cAMP) levels in mesangial cells (25th to 30th passages) nearly threefold. If isobutylmethylxanthine (MIX) was also included, the hormones caused marked further increases in cAMP (after a 20-min incubation, control with MIX, 64.2 ± 5.2 pmoles/mg protein: 10-4 M norepinephrine, 4266 ± 284 pmoles/mg protein; 10-4 M epinephrine, 5812 ± 173 pmoles/mg protein; and 10-4 M isoproterenol, 1336 ± 114 pmoles/mg protein). Under both of these circumstances (that is, catecholamines with or without MIX) greater than 50% of the cells underwent a change in shape (that is, had a round cell body with long, thin tapered processes). The cAMP and shape change response was independent of extracellular calcium ions and appeared to be due to β-adrenergic stimulation. Isoproterenol with MIX stimulated an alteration in morphology and cAMP production at concentrations of 10-4 M to 10-9 M. Within 10 min following β-adrenergic stimulation (10-4 M isoproterenol plus MIX) cAMP was maximum; at this time a shape change was first evident. Eighty-five to one hundred percent of the cells had undergone a shape change by 40 min. Dibutyryl cAMP (10-3 M) also induced a shape change in cultured mesangial cells. The addition of PGE2 to either morphologically altered cells or to the isoproterenol incubation medium (with or without MIX) prior to treating the cells, resulted in complete restoration to the normal flat appearance of mesangial cells or no shape change, respectively. PGE2 attenuated but did not abolish hormone-induced elevations in intracellular cAMP. Thus, catecholamines caused mesangial cells to change their shape in association with elevations of intracellular cAMP. PGE2 markedly inhibited the shape changes as well as markedly attenuated cAMP generation.
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