Adenylyl cyclase isoforms and signal integration in models of vascular smooth muscle cells

Webb, Jerry G.; Yates, Phillip W.; Yang, Qing; Mukhin, Y.; Lanier, Stephen M.

doi:10.1152/ajpheart.2001.281.4.h1545

Cited by 33 publications

(33 citation statements)

References 34 publications

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“…Previous data using heterologously expressed protein indicate that AC3 stimulation by Ca 2ϩ is dependent upon coincidental activation of AC by either G s or forskolin (18), results consistent with what we observe in cardiac fibroblasts. An important role for a Ca 2ϩ -stimulable AC isoform in the observed cross-talk is inferred by data from vascular smooth muscle (33) and directly supported by our studies overexpressing AC6. By increasing AC6 expression, we altered the balance of AC isoform expression in favor of an isoform not stimulated by Ca 2ϩ and found that the G q -G s cross-talk was fractionally reduced.…”

Section: Discussionsupporting

confidence: 80%

Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin

Ostrom¹,

Naugle

Hase³

et al. 2003

Journal of Biological Chemistry

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Cardiac fibroblasts regulate formation of extracellular matrix in the heart, playing key roles in cardiac remodeling and hypertrophy. In this study, we sought to characterize cross-talk between G q and G s signaling pathways and its impact on modulating collagen synthesis by cardiac fibroblasts. Angiotensin II (ANG II) activates cell proliferation and collagen synthesis but also potentiates cyclic AMP (cAMP) production stimulated by ␤-adrenergic receptors (␤-AR). The potentiation of ␤-AR-stimulated cAMP production by ANG II is reduced by phospholipase C inhibition and enhanced by overexpression of G q . Ionomycin and thapsigargin increased intracellular Ca 2؉ levels and potentiated isoproterenoland forskolin-stimulated cAMP production, whereas chelation of Ca 2؉ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/AM inhibited such potentiation. Inhibitors of tyrosine kinases, protein kinase C, or G␤␥ did not alter this cross-talk. Immunoblot analyses showed prominent expression of adenylyl cyclase 3 (AC3), a Ca 2؉ -activated isoform, along with AC2, AC4, AC5, AC6, and AC7. Of those isoforms, only AC3 and AC5/6 proteins were detected in caveolin-rich fractions. Overexpression of AC6 increased ␤AR-stimulated cAMP accumulation but did not alter the size of the ANG II potentiation, suggesting that the cross-talk is AC isoform-specific. Isoproterenol-mediated inhibition of serum-stimulated collagen synthesis increased from 31 to 48% in the presence of ANG II, indicating that ␤AR-regulated collagen synthesis increased in the presence of ANG II. These data indicate that ANG II potentiates cAMP formation via Ca 2؉ -dependent activation of AC activity, which in turn attenuates collagen synthesis and demonstrates one functional consequence of crosstalk between G q and G s signaling pathways in cardiac fibroblasts.

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Section: Discussionsupporting

confidence: 80%

Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin

Ostrom¹,

Naugle

Hase³

et al. 2003

Journal of Biological Chemistry

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“…42,43 AVP treatment can amplify cAMP production when vascular smooth muscle cells are treated with a ␤-adrenoceptor agonist, although AVP alone does not elevate cAMP. 44 This effect is blocked by V 1a , but not V 2 antagonists, and appears to be dependent on the AVPinduced rise in [Ca 2ϩ ] i . 44,45 Some such signal cross-talk may explain the observations in our experiments.…”

Section: Discussionmentioning

confidence: 92%

cAMP/PKA-Dependent Increases in Ca Sparks, Oscillations and SR Ca Stores in Retinal Arteriolar Myocytes after Exposure to Vasopressin

Jeffries

McGahon

Bankhead

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the effects of arginine vasopressin (AVP) on Ca 2ϩ sparks and oscillations and on sarcoplasmic reticulum (SR) Ca 2ϩ content in retinal arteriolar myocytes. METHODS.Fluo-4-loaded smooth muscle in intact segments of freshly isolated porcine retinal arteriole was imaged by confocal laser microscopy. SR Ca 2ϩ store content was assessed by recording caffeine-induced Ca 2ϩ transients with microfluorimetry and fura-2. RESULTS. The frequencies of Ca 2ϩ sparks and oscillations were increased both during exposure to, and 10 minutes after washout of AVP (10 nM). Caffeine transients were increased in amplitude 10 and 90 minutes after a 3-minute application of AVP. Both AVP-induced Ca 2ϩ transients and the enhancement of caffeine responses after AVP washout were inhibited by SR 49059, a V 1a receptor blocker. Forskolin, an activator of adenylyl cyclase, also persistently enhanced caffeine transients. Rp-8-HA-cAMPS, a membrane-permeant PKA inhibitor, prevented enhancement of caffeine transients by both AVP and forskolin. Forskolin, but not AVP, produced a reversible, Rp-8-HA-cAMPS insensitive reduction in basal [Ca 2ϩ ] i .CONCLUSIONS. AVP activates a cAMP/PKA-dependent pathway via V 1a receptors in retinal arteriolar smooth muscle. This effect persistently increases SR Ca 2ϩ loading, upregulating Ca 2ϩ sparks and oscillations, and may favor prolonged agonist activity despite receptor desensitization. (Invest Ophthalmol Vis Sci. 2010;51:1591-1598

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“…Conversely, relaxations to both agents were potentiated by inhibition of cAMP hydrolysis with IBMX. Although this phosphodiesterase inhibitor also unmasked a small concentration-dependent direct relaxant response to A-23187 in rings without endothelium, presumably by weakly stimulating the Ca 2ϩ -activated type VIII adenylyl cyclase isoform (31), submaximal relaxations of endothelium-intact rings to A-23187 were amplified by up to to threefold in the presence of IBMX. Responses to ACh and A-23187 were inhibited by the combination of apamin plus charybdotoxin, even when relaxation was potentiated by IBMX.…”

Section: Discussionmentioning

confidence: 95%

Gap junction-dependent and -independent EDHF-type relaxations may involve smooth muscle cAMP accumulation

Chaytor

Taylor

Griffith

2002

American Journal of Physiology-Heart and Circulatory Physiology

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We have compared the mechanisms that contribute to endothelium-derived hyperpolarizing factor (EDHF)-type responses induced by ACh and the Ca2+ ionophore A-23187 in the rabbit iliac artery. Relaxations to both agents were associated with ∼1.5-fold elevations in smooth muscle cAMP levels and were attenuated by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (DDA) and potentiated by the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Mechanical responses were inhibited by coadministration of the Ca2+-activated K+channel blockers apamin and charybdotoxin, both in the absence and presence of IBMX, but were unaffected by blockade of ATP-sensitive K+ channels with the sulphonylurea glibenclamide. Relaxations and elevations in cAMP evoked by ACh were abolished by 18α-glycyrrhetinic acid, which disrupts gap junction plaques, whereas the corresponding responses to A-23187 were unaffected by this agent. Consistently, in “sandwich” bioassay experiments, A-23187, but not ACh, elicited extracellular release of a factor that evoked relaxations that were inhibited by DDA and potentiated by IBMX. These findings provide evidence that EDHF-type relaxations of rabbit iliac arteries evoked by ACh and A-23187 depend on cAMP accumulation in smooth muscle, but involve signaling via myoendothelial gap junctions and the extracellular space, respectively.

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Adenylyl cyclase isoforms and signal integration in models of vascular smooth muscle cells

Cited by 33 publications

References 34 publications

Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin

Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin

cAMP/PKA-Dependent Increases in Ca Sparks, Oscillations and SR Ca Stores in Retinal Arteriolar Myocytes after Exposure to Vasopressin

Gap junction-dependent and -independent EDHF-type relaxations may involve smooth muscle cAMP accumulation

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