Effect of pituitary adenylate cyclase activating polypeptide on vasopressin-induced proliferation of aortic smooth muscle cells: comparison with vasoactive intestinal polypeptide

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) inhibited dose dependently the DNA synthesis stimulated by arginine vasopressin (AVP) in cultured rat aortic smooth muscle cells (SMC). The inhibition was cell cycle dependent and the maximum inhibition was observed when added at the late G1 phase of the cell cycle. Vasoactive intestinal polypeptide (VIP), which shows a considerable homology with PACAP, also inhibited dose dependently the AVP-induced DNA synthesis in a cell cycle dependent manner. The maximum inhibition was also observed at the late G1 phase. The patterns of both the dose-dependent inhibitions were similar, and the inhibition by a combination of PACAP and VIP was not additive. PACAP stimulated dose dependently cAMP accumulation in aortic SMC. VIP also stimulated cAMP accumulation, and the accumulation by a combination of PACAP and VIP was not additive. Both PACAP and VIP had little effect on phosphoinositide hydrolysis in these cells. The suppression of the AVP-induced DNA synthesis by PACAP or VIP was enhanced by 3-isobutyl-1-methylxanthine, an inhibitor for phosphodiesterases. Dibutyryl cAMP, but not 8-bromo-cGMP, inhibited the AVP-induced DNA synthesis, and a combination of PACAP and dibutyryl cAMP was not additive. [Ac-Tyr1,D-Phe2]growth hormone-releasing factor, an antagonist for VIP receptor, reversed the inhibitory effect of PACAP on the AVP-induced DNA synthesis. These results suggest that PACAP has an antiproliferative effect on aortic SMC at the late G1 phase of the cell cycle through cAMP production, and that PACAP and VIP inhibit the AVP-induced DNA synthesis by a common mechanism.

Interleukin‐4 blocks thapsigargin‐induced cell death in rat rod photoreceptors: Involvement of cAMP/PKA pathway

“…Similar to other cell types (Taieb et al, 1991; Vazquez et al, 1991; Galéa et al, 1993), IL‐4 increased the cAMP intracellular levels in retinal cells. Both IL‐4 and cAMP have been reported to inhibit proliferation vascular smooth muscle cells and retinal cells (Southgate and Newby, 1990; Oiso et al, 1993; Vadiveloo et al, 1997; Silva et al, 2008), and abundant data are available showing that increased levels of cAMP can inhibit proliferation and trigger differentiation in various cell types through the activation of PKA (Sherwood et al, 2000; Stork and Schmitt, 2002; Fogarty et al, 2007; Silva et al, 2008). In addition, it has been shown that proliferation of human B cells stimulated by IL‐2, anti‐μ mAb DA44, or phorbol ester is inhibited by IL‐4 and involves PKA activation (Taieb et al, 1991; Vazquez et al, 1991).…”

Rat Aortic Smooth‐Muscle Cell Proliferation Is Bidirectionally Regulated in a Cell Cycle‐Dependent Manner via PACAP/VIP Type 2 Receptora

“…These results are in agreement with the previous report in which PACAP inhibited the vasopressin‐induced proliferation of rat aortic smooth muscle cell. 16…”

“…These results are in agreement with the previous report in which PACAP inhibited the vasopressin-induced proliferation of rat aortic smooth muscle cell. 16 Thus in the 24-h [ 3 H]thymidine incorporation assay, PACAP enhanced FCS-induced DNA synthesis when added at G 0 /G 1 phase of the cell cycle. In contrast, PACAP exhibited a suppressive effect when added at the late G 1 phase.…”

VIP Gene Deletion in Mice Causes Cardiomyopathy Associated with Upregulation of Heart Failure Genes

“…While the effects of VIP on smooth muscle proliferation are well-known [9]–[14], the effect on striated muscle has not been well-studied. Our study is the first to test the effect of loss of the VIP gene on striated left and right ventricular muscle and function, supporting the role for VIP as potential therapeutic option in cardiomyopathy.…”