title: Adreno-muscarinic synergy in the bladder trigone: calcium-dependent and -independent mechanisms.
abstract: We have recently demonstrated a strong synergy between both excitatory pathways in the trigone which--as part of the bladder base--is believed to play a key role in outflow control. The aim of this study was to reveal whether modulation of intracellular Ca2+, [Ca2+]i, is mainly responsible for this synergistic effect. Intact muscle strips from the superficial trigone of male guinea-pigs were used for tension experiments. In isolated trigonal cells, [Ca2+]i was measured by epifluorescence microscopy using the fluorescent Ca2+-indicator Fura-2. Phenylephrine (PE, 10 microM) augmented contractions induced by carbachol (1 microM) to 4.0+/-0.8-fold of control, while corresponding [Ca2+]i levels did not exceed 1.3+/-0.2-fold of control. Furthermore, PE generated significantly greater contractions for a given rise of [Ca2+]i, compared to depolarising KCl solutions. The protein kinase C inhibitor GF 109203X (5 microM) and the Rho-kinase inhibitor Y-27632 (5microM) reduced the PE contracture to 37.3+/-9.4 and 60.1+/-12.4% of control, respectively, without significantly altering the [Ca2+]i transients. GF 109203X reduced the augmentation of 1microM carbachol by PE to 1.5+/-0.1-fold. Muscarinic and adrenergic receptor activation exerts a strong synergistic effect in the bladder trigone without similar changes to the [Ca2+]i transient. Ca2+-sensitisation of contractile proteins is likely to play a key role in this synergism, particularly for adrenergic activation.
authors.affiliation: Department of Surgery, University College London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roosen
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Fry
authors.forename: Guiping
authors.initials: G
authors.lastname: Sui
authors.forename: Changhao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction; D001743:Urinary Bladder / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; D007211:Indoles; D008301:Maleimides; D011725:Pyridines; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; C108830:Y 27632; D010656:Phenylephrine; D002217:Carbachol; D054460:rho-Associated Kinases; D011493:Protein Kinase C; C070515:bisindolylmaleimide I