Effect of omega conotoxin on reflex responses mediated by activation of capsaicin-sensitive nerves of the rat urinary bladder and peptide release from the rat spinal cord.
The aim of this study was to assess whether omega conotoxin fraction GVIA, a potent blocker of N- and L-type voltage-sensitive calcium channels, might interfere with reflex responses (micturition, blood pressure rise in spinal rats) produced by activation of capsaicin-sensitive sensory nerves of the rat urinary bladder. The effect of conotoxin was also investigated on reflex micturition persisting after capsaicin pretreatment. Following topical application onto the bladder, conotoxin did not affect the volume threshold to elicit micturition although it reduced the amplitude of volume-evoked bladder contractions. Likewise, topical conotoxin did not prevent the reflex rise in blood pressure elicited by sudden bladder distension or topical application of capsaicin onto the bladder. In contrast, topical lidocaine strongly prevented both reflex responses. After intrathecal administration, conotoxin produced a dose-dependent inhibition of volume-evoked bladder contractions and the cardiovascular reflex produced by mechanical or chemical stimulation of bladder nerves. Intrathecal conotoxin inhibited micturition also in rats pretreated with capsaicin (50 mg/kg s.c., 4 days before). Depolarization by high potassium (80 mM) produced release of both substance P- and calcitonin gene-related peptide-like immunoreactivity from superfused slices of the dorsal half of rat spinal cord. Capsaicin (1 microM) produced a similar effect, and a previous exposure to capsaicin prevented the effect of potassium. Conotoxin (0.1 microM) significantly reduced (about 50%) the potassium-induced release of neuropeptides from the dorsal half of the rat spinal cord. These findings indicate that conotoxin-sensitive calcium channels in the rat spinal cord play a role in the neurotransmission along reflex pathways activated by stimulation of capsaicin-sensitive nerves in the urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
Maggi
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CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
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Santicioli
P
P
Tramontana
M
M
Meli
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D020916:Conotoxins; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D014554:Urination / Q000187:drug effects*
D002121:Calcium Channel Blockers; D020916:Conotoxins; D008978:Mollusk Venoms; C055407:conotoxin GV; D002211:Capsaicin