Novel model for “calcium paradox” in sympathetic transmission of smooth muscles: Role of cyclic AMP pathway

• Published in: Cell calcium (Edinburgh) Vol. 54; no. 3; pp. 202 - 212
• Main Authors: Bergantin, Leandro Bueno, Souza, Cláudio Fontes, Ferreira, Regiane Miranda, Smaili, Soraya Soubhi, Jurkiewicz, Neide Hyppolito, Caricati-Neto, Afonso, Jurkiewicz, Aron
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2013
• Subjects: Adenylyl Cyclases - metabolism; Advanced Basic Science; Animals; Calcium; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - chemistry; Calcium Channels, L-Type - metabolism; cAMP; Cyclic AMP - metabolism; Enzyme Inhibitors - pharmacology; Male; Models, Biological; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Rats; Rats, Wistar; Smooth muscle; Sympathetic transmission; Thapsigargin - pharmacology; Vas Deferens - drug effects; Vas Deferens - physiology; Smooth muscle; Calcium; cAMP; Sympathetic transmission
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2013.06.004

Abstract It is well established that reduction of Ca2+ influx through L-type voltage-dependent Ca2+ channel (L-type VDCC), or increase of cytosolic cAMP concentration ([cAMP]c), inhibit contractile activity of smooth muscles in response to transmitters released from sympathetic nerves. Surprisingly, in this work we observed that simultaneous administration of L-type VDCC blocker (verapamil) and [cAMP]c enhancers (rolipram, IBMX and forskolin) potentiated purinergic contractions evoked by electrical field stimulation of rat vas deferens, instead of inhibiting them. These results, including its role in sympathetic transmission, can be considered as a “calcium paradox”. On the other hand, this potentiation was prevented by reduction of [cAMP]c by inhibition of adenylyl cyclase (SQ 22536) or depletion of Ca2+ storage of sarco-endoplasmic reticulum by blockade of Ca2+ reuptake (thapsigargin). In addition, cytosolic Ca2+ concentration ([Ca2+ ]c ) evaluated by fluorescence microscopy in rat adrenal medullary slices was significantly reduced by verapamil or rolipram. In contrast, simultaneous incubation of adrenal slices with these compounds significantly increased [Ca2+ ]c . This effect was prevented by thapsigargin. Thus, a reduction of [Ca2+ ]c due to blockade of Ca2+ influx through L-type VDCC could stimulate adenylyl cyclase activity increasing [cAMP]c thereby stimulating Ca2+ release from endoplasmic reticulum, resulting in augmented transmitter release in sympathetic nerves and contraction.