NANC neurotransmission in lamina propria of the rabbit urethra: regulation by different subsets of calcium channels

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Abstract

Electrical field stimulation (EFS) of the rabbit urethral lamina propria elicited a frequency‐dependent non‐adrenergic, non‐cholinergic (NANC) relaxation, which was abolished by NΩ–nitro‐L‐arginine (l‐NOARG). Ω‐Conotoxin GVIA, a selective blocker of N‐type voltage‐operated calcium channels (VOCCs), and Ω‐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 co‐conotoxin GVIA alone. The relaxation induced by the nitric oxide (NO) donor, 3‐morpholino‐sydnonimine (SIN‐1) was not affected by Ω‐conotoxin MVIIC. Ω‐Agatoxin IVA (blocker of P‐type VOCCs) did not attenuate the NANC relaxation. 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. EFS (20Hz, 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. 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. It is suggested that nitrergic nerve activation in the rabbit urethral lamina propria is mediated in part by N‐type (co‐conotoxin GVIA‐sensitive) and in part by Q‐type (co‐conotoxin MVIIC‐sensitive) VOCCs. With high frequences of stimulation, another mechanism, possibly calcium‐independent, appears to become operational. 1995 British Pharmacological Society

Detaljer

Författare
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1020-1026
Antal sidor7
TidskriftBritish Journal of Pharmacology
Volym115
Utgivningsnummer6
StatusPublished - 1995 jan 1
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa