Spontaneous beating of rabbit sinoatrial node cells (SANCs) is controlled by cAMP-mediated, protein kinase A–dependent local subsarcolemmal ryanodine receptor Ca releases (LCRs). LCRs activated an inward Na /Ca exchange current that increases the terminal diastolic depolarization rate and, therefore, the spontaneous SANC beating rate. Basal cAMP in SANCs is elevated, suggesting that cAMP degrad...

Epilepsy is a neurological disorder. Phosphodiesterase (PDE) enzymes are responsible for the hydrolysis of the cyclic nucleotides and therefore have a critical role in regulating intracellular levels of the second messengers cAMP, cGMP, and hence cell function as well as downstream signaling in the various body systems This study was conducted to evaluate the effect of phosphodiesterase isozyme...

Spontaneous beating of rabbit sinoatrial node cells (SANCs) is controlled by cAMP-mediated, protein kinase A-dependent local subsarcolemmal ryanodine receptor Ca(2+) releases (LCRs). LCRs activated an inward Na(+)/Ca(2+) exchange current that increases the terminal diastolic depolarization rate and, therefore, the spontaneous SANC beating rate. Basal cAMP in SANCs is elevated, suggesting that c...

This study aimed to characterize the cellular pathways along which nitric oxide (NO) stimulates renin secretion from the kidney. Using the isolated perfused rat kidney model we found that renin secretion stimulated 4- to 8-fold by low perfusion pressure (40 mmHg), by macula densa inhibition (100 micromol/liter of bumetanide), and by adenylate cyclase activation (3 nmol/liter of isoproterenol) w...

We studied the activation of 3',5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) by using a cell-permeant enzyme inhibitor. Rods of Ambystoma tigrinum held in a suction electrode were jumped into a stream of 3-isobutyl-1-methylxanthine (IBMX), 0.01-1 mM. Initial transient light-sensitive currents fit the notion that dark and light-activated forms of PDE contributed independently...

Initial sweet taste transduction is expected to occur in the subsecond time range. We demonstrate a rapid and transient (75-250 ms) increase of cGMP (but not cAMP) level in rat intact circumvallate taste cells after stimulation by sucrose. This rapid increase does not occur in nonsensory epithelial cells. Pretreatment with a nonspecific phosphodiesterase (PDE) inhibitor (IBMX), a specific cAMP-...

Tadalafil is PDE5 inhibitor that has recently been approved for the treatment of ED. The mechanism of action of tadalafil is similar to sildenafil and vardenafil through the inhibition of PDE. In both chemical structure and PDE subtype selectivity profile, tadalafil differs markedly from sildenafil and vardenafil. Compared with sildenafil and vardenafil, tadalafil exhibits a prolonged plasma re...