*  Isolation and characterization of single vascular smooth muscle cells from spontaneously hypertensive rats. | Hypertension
To study the properties of vascular smooth muscle in hypertension without the influence of the nerves and endothelium, a procedure was developed to isolate single smooth muscle cells from tail arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive control rats. Perfusion of intact arteries with a solution of papain and collagenase produced dense populations of viable cells (more than 10(4) cells/ml) that remained relaxed in the presence of physiological levels of calcium. Contractile responses of smooth muscle cells from the SHR were significantly more sensitive to noradrenaline, potassium depolarization, and the calcium channel agonist Bay K 8644 compared with those from WKY rats. Enhanced sensitivity to calcium in the SHR was also observed on readdition of calcium to cells preincubated in noradrenaline or KCl in a calcium-free medium. These results provide evidence for ...
  http://hyper.ahajournals.org/content/14/2/137
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The use of TIR-FM enabled us to visualize the steady state and calcium-induced submembrane movement, docking, and fusion of intracellular compartments to the plasma membrane. We found that calcium ionophore A23187 induced increase in calcium did not cause exocytosis of Golgi, ER, early, or late endosomes, and did not lead to an increase in exocytosis of post-Golgi vesicles. The absence of an effect of calcium on exocytosis of early endosomes is in agreement with the previously reported absence of an affect of calcium increase on transferrin recycling (Rodriguez et al., 1997). On the other hand, absence of an effect of calcium on exocytosis of Golgi and Golgi-derived vesicles is contrary to the proposed role of Golgi derived compartments in Ca2+-induced exocytosis in fibroblasts (Togo et al., 1999).. An increase in calcium caused either by the calcium ionophore A23187 or by ...
  http://jcb.rupress.org/content/159/4/625.long
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Adenophostin A is a glyconucleotide natural product with the highest known potency for the D-myo-inositol 1,4,5-trisphosphate receptor. Using synthetic adenophostin A we have investigated the macroscopic and microscopic protonation process of this compound by performing (31)P NMR, (1)H NMR, and potentiometric titration experiments. The logarithms of the first to the fourth stepwise protonation constants are, respectively, log K(1) = 8.48, log K(2) = 6.20, log K(3) = 4.96, and log K(4) = 3.80. The latter constant refers to the protonation equilibrium involving the N1 adenine nitrogen. From the microconstants the protonation fractions of each individual phosphate group can be calculated. Remarkably, the ionization state of the phosphates of adenophostin A at near physiological pH is very similar to those of inositol 1,4,5-trisphosphate, indicating that differences in phosphate charge cannot account for the high potency of this molecule. The analysis of the (1)H chemical shifts vs pH provided complementary
  https://pharm.ox.ac.uk/publications/678619
*  Plus it
With PDEs inactivated by IBMX, we assume that there are two pathways for inhibition of ICa(L) by cGMP/PKG, namely, phosphorylation of the α1c subunit that antagonizes the stimulant effect of cAMP/PKA and/or activation of PP that dephosphorylates the α1c subunit. Can 8-Br-cGMP or CCh suppress Ca2+ current through L-type channels in the presence of ATPγS, which allows kinases to thiophosphorylate substrates that resist phosphatase action? Irreversible suppression by 8-Br-cGMP would indicate that thiophosphorylation of the channel had occurred at a site different from that acted upon by cAMP/PKA (Méry et al., 1991; Sumii and Sperelakis, 1995). Alternatively, failure of 8-Br-cGMP to suppress ICa(L) in ATPγS would indicate that the thiophosphorylated channel was resistant to phosphatase. Our results are consistent with the PP hypothesis for inhibition by cGMP of current through L-type channels in guinea pig ventricular myocytes.. Neurotransmitter ...
  http://jpet.aspetjournals.org/content/301/2/501
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BAYK 8644 is a L-type Ca2+ channel activator (EC50 = 17.3 nM). BAYK 8644 has positive inotropic, vasoconstrictive and behavioral effects in vivo.
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*  Research programme: potassium channel agonists - 4SC - AdisInsight
4SC was developing small molecule openers of the human Ca2+-activated and voltage-dependent potassium channel BKCa as potential therapeutics for the treatment
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The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
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*  Bicyclic analogues of inositol 1,4,5-trisphosphate based upon adenophostin A - Opus
Riley, A. M. and Potter, B. V. L., 1999. Bicyclic analogues of inositol 1,4,5-trisphosphate based upon adenophostin A. Tetrahedron Letters, 40 (11), pp. 2213-2216.. ...
  http://opus.bath.ac.uk/32169/
*  adenophostin A | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY
The IUPHAR/BPS Guide to Pharmacology. adenophostin A ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
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Bay St. Biergarten Yappy Hour This happy hour event encourages patrons to bring their dogs to the pooch-friendly patio at Bay St. Biergarten. Drink specials include $1 off all draft beers and $3 off specialty cocktails. The event will feature discounted appetizers including $3 pretzels, $4 fried pickles and $5 wings.
  https://www.charlestoncitypaper.com/charleston/bay-st-biergarten-yappy-hour/Event?oid=5175222
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