title: NANC neurotransmission in lamina propria of the rabbit urethra: regulation by different subsets of calcium channels.
abstract: 1. Electrical field stimulation (EFS) of the rabbit urethral lamina propria elicited a frequency-dependent non-adrenergic, non-cholinergic (NANC) relaxation, which was abolished by N omega-nitro-L-arginine (L-NOARG). 2. omega-Conotoxin GVIA, a selective blocker of N-type voltage-operated calcium channels (VOCCs), and omega-conotoxin MVIIC (blocker of N- and Q-type VOCCs) inhibited the NANC relaxation, and the inhibition was inversely related to the frequency of stimulation. Combined, the two toxins were more effective than omega-contoxin GVIA alone. 3. The relaxation induced by the nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1) was not affected by omega-conotoxin MVIIC. 4. omega-Agatoxin IVA (blocker of P-type VOCCs) did not attenuate the NANC relaxation. 5. Reduction of the calcium concentration from 1.5 to 0.5 mM reduced the NANC relaxation at low but not at high frequencies of stimulation; the relaxation induced by SIN-1 was not affected. 6. EFS (20 Hz, 30 s) increased the cyclic GMP level 3 fold in normal Krebs solutions, but was unable to enhance significantly the cyclic GMP level after calcium omission. L-NOARG reduced the cyclic GMP content in 'calcium-free' medium, indicating an ongoing NO synthesis that was independent of extracellular calcium. 7. Caffeine, ryanodine and thapsigargin (inhibitors of sarcoplasmic calcium release), and CGP 37157 (inhibitor of mitochondrial sodium/calcium exchange) had no effect on the NANC relaxation. 8. It is suggested that nitrergic nerve activation in the rabbit urethral lamina propria is mediated in partby N-type (omega-conotoxin GVIA-sensitive) and in part by Q-type (omega-conotoxin MVIIC-sensitive) VOCCs.With high frequences of stimulation, another mechanism, possibly calcium-independent, appears to become operational.
authors.affiliation: Department of Clinical Pharmacology, Lund University Hospital, Sweden.
authors.forename: P K
authors.initials: PK
authors.lastname: Zygmunt
authors.forename: P M
authors.initials: PM
authors.lastname: Zygmunt
authors.forename: E D
authors.initials: ED
authors.lastname: Högestätt
authors.forename: K E
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification* / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D019335:Nitroarginine; D011817:Rabbits; D014521:Urethra / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D001120:Arginine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium