title: Novel model for "calcium paradox" in sympathetic transmission of smooth muscles: role of cyclic AMP pathway.
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.
authors.affiliation: Department of Pharmacology, INFAR--Escola Paulista de Medicina, Federal University of São Paulo, Brazil.
authors.forename: Leandro Bueno
authors.initials: LB
authors.lastname: Bergantin
authors.forename: Cláudio Fontes
authors.initials: CF
authors.lastname: Souza
authors.forename: Regiane Miranda
authors.initials: RM
authors.lastname: Ferreira
authors.forename: Soraya Soubhi
authors.initials: SS
authors.lastname: Smaili
authors.forename: Neide Hyppolito
authors.initials: NH
authors.lastname: Jurkiewicz
authors.forename: Afonso
authors.initials: A
authors.lastname: Caricati-Neto
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium
keywords: Calcium; Smooth muscle; Sympathetic transmission; cAMP