Neurochemical evidence for the involvement of N-type calcium channels in transmitter secretion from peripheral endings of sensory nerves in guinea pigs.
In the guinea pig ureter, substance P-(SP) and calcitonin gene-related peptide-(CGRP) like immunoreactivity (LI) were depleted by systemic capsaicin pretreatment, indicating that they are entirely stored in peripheral endings of primary afferent neurons. Electrical field stimulation (20 Hz, 60 V, 0.5 ms) evoked the simultaneous release of SP- and CGRP-LI from superfused guinea pig ureters which was abolished by tetrodotoxin (0.3 microM). omega-Conotoxin (0.1 microM), a potent blocker of N-type voltage-sensitive calcium channels, reduced by 50-70% the evoked release of both peptides. These findings provide direct neurochemical evidence indicating that conotoxin-sensitive calcium channels play a role in transmitter secretion evoked by antidromic invasion of peripheral terminals of capsaicin-sensitive primary afferents.
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
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Maggi
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Tramontana
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Cecconi
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D013373:Substance P; D013779:Tetrodotoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin