体外循环期间血浆环核苷酸变化的临床研究

本文对14例体外循环下心内直视手术病人采用放免法,于不同时段测定体外循环转流期间血浆的环核苷酸cAMP 和cGMP 变化。结果表明,在体外循环期间,cAMP和cGMP 浓度进行性上升,转流结束时达到最高峰,随着自身循环的恢复,cAMP 和cGNP浓度逐渐下降,术后次日恢复到术前水平;而cAMP/cGMP 比值在体外循环期间无明显变化。文中讨论了cAMP 和cGMP 变化的机制和临床意义。     

蛇毒溶栓素对实验动物血小板功能和环腺苷酸含量的影响

本文报道蛇毒溶栓素对实验动物血小板功能和血浆环腺苷酸含量的影响.(1)对血小板数的影响:给家犬以4 u/kg量静注1小时后,循环血的血小板数由药前130.44×10~9/L±50.02×10~9/L下降至60.20×10~9/L±20.50×10~9/L(P<0.05).(2)对血小板聚集功能的影响:猕猴和家兔分别按4 u/kg、8 u/kg量静注1小时后,对ADP诱导的血小板聚集率分别山药前的62.32±22.05%和43.66±10.60%下降至1.32±0.49%和4.95±1.96%;抑制率分别为97.50±1.75%和88.34±4.31%,与药前组相比均有非常显著的差异(P<0.001).(3)对血小板cAMP含量的影响:猕猴和家兔以蛋白竞争结合法测定血小板内cAMP的含量,药后1小时的含量65.43±31.35pmole/mg,32.25±15.43pmo1e/mg蛋白质,与药前12.02±0.95pmole/mg,4.25±3.13pmole/mg蛋白质相比有明显升高(P<0.001).     

Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation

The effect of prostaglandin E₁ (PGE₁) on platelets is mediated through the PGE₁ receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE₁ and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 gm. The time course of the extension length (Dp, in μg) of the platelets in response to aspiration with a negative pressure (ΔP) of 5 cm H₂ O (ΔP × Rp = 0.15 dynes/cm) was analyzed. PGE₁ treatment (0.1 μM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE₁ -treated) / Dp/Rp (control), was significantly reduced to 0.90 ± 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE₁ -treated platelets had a higher [cAMP]_i than controls. Platelets treated with PGE₁ or dbcAMP showed a reduced [Ca²⁺]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE₁ and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]_i and low [Ca²⁺]_i after PGE₁ treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.     

Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

 To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca²⁺ currents (I _Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I _Ca,L was recorded by a step-pulse protocol after eliminating K⁺ conductances (internal Cs⁺ plus tetraethylammonium chloride and K⁺-free extracellular solution). A-II (100 nM) did not affect basal I _Ca,L, but inhibited I _Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I _Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT₁) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I _Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I _Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT₁ receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Dopamine receptors on human T- and B-lymphocytes

The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[³H]sulpride as a ligand to detect the presence of recognition sites of the dopamine D₂ receptor family on human T- and B-lymphocytes. The (-)-[³H]sulpiride binding was of high affinity (K_d 0.9 nM ± 0.2 nM, specific, saturable (B_max 10.2 ± 1.4 fmol/10⁶ cells) and reversible. The pharmacological characterization of the recognition site suggests, similarities mainly with the D₂ and D₄ rather than D₃ subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions.