Retinoic acid and triiodothyronine stimulate ADP-ribosyl cyclase activity in rat vascular smooth muscle cells

Cyclic ADP-ribose (cADPR) is a nucleotide synthesized from beta-NAD(+) that can trigger or facilitate Ca2+- release through ryanodine-channels. We investigated the synthesis of cADPR (ADPR-cyclase activity) in cultured vascular smooth muscle cells (VSMC) from rat aorta in response to incubation with all-trans-retinoic acid (RA), 3,3',5'-triiodothyronine (T-3), cortisol, beta-estradiol and 1-dehydrotestosterone. Only RA and T-3 caused concentration-dependent (10(-9) - 10(-6) M) stimulation of ADPR-cyclase activity in VSMC. Maximum stimulatory responses to RA (+100%) and T-3 (+40%) were additive and the stimulatory effects of both hormones on ADPR-cyclase were due to an increase in Vmax without changes in the apparent Km. These observations indicate that in VSMC synthesis of cADPR can be upregulated by RA and T-3. We propose that some of the actions of RA on VSMC such as enhancement of contractile competence, differentiation, and anti-proliferative effects might be elicited, at least in part, via upregulation of the cADPR/Ca2+-release signaling system. (C) 1997 Academic Press.