Cyclic nucleotide analogs were used to study relaxation of pig coronary arteries and guinea tracheal smooth muscle in an attempt determine the roles cAMP- cGMP-dependent protein kinases (cA-K cG-K). In artery strips, cGMP generally more effective than cAMP promoting K+-induced contractions. Significant this tissue was caused primarily by those cyclic that had high affinities for purified cG-K but not cA-K. The low potencies cA-K-specific analogs, as compared with cG-K-specific could be...

This study was conducted to evaluate the possibility of selective inhibition either guanosine cyclic 39,59-monophosphate or adenosine phosphodiesterase activities pig coronary arteries. Two peaks (I and II) nucleotide activity a heat-stable, nondialyzable activator peak I can be resolved from intima plus media layer arteries by DEAE-cellulose chromatography. Peak catalyzes hydrolysis both GMP AMP, but it has much lower apparent K m (1-4 µM) for than AMP (40-100 µM). II is relatively specific...

Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts cGMP-dependent protein kinase isozymes (cGMP I alpha and beta). In order to understand the roles these in relaxing vascular smooth muscle, several new cGMP analogs were synthesized tested for potencies activating each enzyme arteries. Analogs modified with a derivatized phenylthio group at 8-position as much 72-fold more potent purified than beta. Electron-donating substituents, such hydroxy,...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective inhibition of cyclic nucleotide phosphodiesterases by analogs 1-methyl-3-isobutylxanthineG. L. Kramer, J. E. Garst, S. Mitchel, and N. WellsCite this: Biochemistry 1977, 16, 15, 3316–3321Publication Date (Print):July 26, 1977Publication History Published online1 May 2002Published inissue 26 July 1977https://doi.org/10.1021/bi00634a006RIGHTS & PERMISSIONSArticle Views135Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the...

Biochemical events associated with activation of smooth muscle contraction were studied in neurally stimulated bovine tracheal muscle. A latency period 500 ms preceded increases isometric force and myosin light chain phosphorylation. However, stimulation resulted the rapid hydrolysis inositol phospholipids as demonstrated by phosphates ms. Inositol trisphosphate increased 2-fold no significant change tetrakisphosphate. The apparent state kinase was assessed indirectly through measurements...

The count of Lagrangian bonding constraints ${n}_{c}(y)$ in ternary ${\mathrm{Ge}}_{25}{\mathrm{S}}_{75\ensuremath{-}y}{\mathrm{I}}_{y}$ glasses $(0<y<0.30)$ is established from the molecular structure using Raman scattering and first-principles cluster calculations. results show that decreases to 3 as y increases close ${y}_{c}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.162(3)$, where a sharply defined global minimum nonreversing heat flow, $\ensuremath{\Delta}{H}_{\mathrm{nr}}(y)$...

T-dependent $^{119}\mathrm{Sn}$ Mossbauer Debye-Waller factor f(T) in ${\mathrm{EuBa}}_{2}$${\mathrm{Cu}}_{2.98}$${\mathrm{Sn}}_{0.02}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ displays evidence of a substantial softening lattice vibrations at T\ensuremath{\le}110 K. In previous $^{151}\mathrm{Eu}$ study, no detectable was found the rare-earth site. These results taken together show that Sn atoms as dilute impurity replace predominantly Cu(1) sites Cu-O chains...

This study identified a series of alkylated xanthines and papaverine analogue with range potencies selectivities as inhibitors phosphodiesterases isolated from bovine coronary arteries. The abilities these to potentiate the relaxant effects sodium nitroprusside (SNP) isoproterenol were predictable inhibit calmodulin-sensitive cyclic AMP-specific forms phosphodiesterase, respectively. Although potentiated SNP- isoproterenol-induced increases in GMP AMP, respectively, manners that consistent...

The xanthines currently represent the most potent class of adenosine receptor antagonists. However, known derivatives xanthine show little difference in antagonist potency between two putative subtypes, A1 and A2. We conducted a systematic study structure-activity relationships that compared at adipocytes with A2 platelets. Since receptors are coupled to adenylate cyclase these tissues, inhibition via stimulation were used as models activation. Antagonist was quantitated by Schild analysis,...

A series of xanthine derivatives and papaverine have been studied to determine their abilities alter tissue levels cyclic AMP GMP, inhibit phosphodiesterase activities, cause relaxation pig coronary arteries. The agents selected for this study exhibited a wide range potencies activities in the artery supernatant fraction. In addition, some these were up 10 times more potent as inhibitors GMP hydrolysis than hydrolysis, while others 2-4 hydrolysis. rank order strips was similar nucleotide...

A series of xanthines with varied substituents in the 1, 3, and 8 positions were prepared an attempt to understand structure--activity relationship for alkylxanthines as inhibitors two different forms cyclic nucleotide phosphodiesterase. Polar on 1 or 3 position xanthine reduced potency inhibit both calmodulin-sensitive "cyclic AMP specific" xanthine, other than a carboxylic acid, increased form phosphodiesterase, if they capable donating electrons nucleus. On hand, any substituent larger H...

We have studied the effects of activators Ca++- and phospholipid-dependent enzyme protein kinase C on isometric tension development by both intact skinned coronary artery strips. The strips contracted upon incubation with 12-O-tetradecanoylphorbol-13-acetate. 12-O-tetradecanoylphorbol-13-acetate produced a leftward shift in concentration-response relationship for contraction tissues K+, histamine norepinephrine. Phorbol-12,13-dibutyrate elicited detergent-skinned when free Ca++ concentration...

Agonist occupation of muscarinic cholinergic receptors 1321N1 human astrocytoma cells results in an activation phosphodiesterase and a resultant 50-75% attenuation isoproterenol-stimulated cyclic AMP accumulation. The effects series inhibitors on receptor-mediated inhibition accumulation the activities partially purified, soluble have been compared to determine which form activity is regulated by receptors. (50 microM) 1-methyl-3-isobutylxanthine (MIX), 1-methyl-3-isobutyl-7-benzylxanthine...

The alpha 2A adrenergic receptor (alpha 2AAR) previously was shown to be directly delivered and retained on the lateral subdomain of renal epithelial cells. present studies demonstrate that, in contrast, wild-type epitope-tagged canine A1 adenosine receptors (A1AdoR) are apically enriched (65-83%) Madin-Darby kidney (MDCKII) porcine (LLC-PKI) cells, based surface biotinylation strategies detecting photoaffinity-labeled A1AdoR. Confocal microscopy corroborated apical enrichment epitopetagged...

Rat platelets and adipocytes were used as models to investigate alterations of the A2- A1-adenosine receptor-adenylate cyclase system peripheral cells caused by chronic caffeine administration. The maximum effects 5'-N-ethylcarboxamidoadenosine (NECA) stimulate adenylate activity in suspensions platelet membranes inhibit aggregation significantly greater with from caffeine-treated rats than control rats. 1 100 nM prostaglandin E1 also These data suggest that increased ability NECA after...

In sea urchin sperm, the hydrolysis of adenosine 3′,5′-monophosphate (cyclic AMP) appears to be predominantly catalyzed by a protein different from that which catalyzes guanosine GMP). The cyclic GMP phosphodiesterase is located primarily in particulate fraction, whereas AMP found mainly soluble fraction sperm cell homogenate. and phosphodiesterases are inactivated at rates N-ethylmaleimide inhibited degrees various inhibitors. Three fractions (A, B, C) nucleotide activity (as measured 1 µM...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInhibition of separated forms phosphodiesterases from pig coronary arteries by uracils and 7-substituted derivatives 1-methyl-3-isobutylxanthineJ. E. Garst, G. L. Kramer, Y. J. Wu, N. WellsCite this: Med. Chem. 1976, 19, 4, 499–503Publication Date (Print):April 1, 1976Publication History Published online1 May 2002Published inissue 1 April 1976https://pubs.acs.org/doi/10.1021/jm00226a010https://doi.org/10.1021/jm00226a010research-articleACS...