Vasopressin and serotonin are important mediators of vasoconstriction and Ca2+ signals in smooth musclo cells. Upon binding to their respective membrane receptor, cytosolic Ca2+ increases are mediated by release of Ca2+ from intracellular stores through the Iris(l,4,5)P3 pathway. The present studies investigated the action of NO donors and cyclic GMP on cytosolic Ca2+ increases induced by stimulation with vasopressin and serotonin in A7r5 smooth muscle cells. The two hormones show different effects and different sensitivities; con centratjons of vasopressin as low as 100 nM induced a transient cytosolic Ca2+ increase with a rapid deactivation. In contrast, 1 /zM serotonin induce sustained ('a2"" oscillations. Our results reveal a rapid and profound action of NO on Ca2"1 oscillations, Ca2+ release and (V+ influx. The potent NO donor GEA 3162, a l-aryl substituted oxatriazole. rapidly inactivated Ca2+ oscillations induced by serotonin. The action of vasopressin was also rapidly decreased upon addition of GKA 3162. Experiments investigating the effects of 8-Br-cyclic GMP, a non-hydrolyzable, membrane pi-rmeant cGMP analogue, showed a dramatic inhibitory effort on serotonin induced Ca24 oscillations. Absence of external Ca2+ did noi abolish Ca2+ oscillation, indicating that external Ca2+ is not required for l he maintenance of the oscillations. The results suggest that the action of nitric oxide through a cyclic GMP pathway, reflecting directed effects on Ca2+ release or Ca2+ storage. (Supported by MH Grant HL55426 and the Sv-iss XatiotMl Research Foundation).
|Original language||English (US)|
|State||Published - Dec 1 1998|
All Science Journal Classification (ASJC) codes
- Molecular Biology