The neurotransmitter role of calcitonin gene-related peptide in the rat and guinea-pig ureter: effect of a calcitonin gene-related peptide antagonist and species-related differences in the action of omega conotoxin on calcitonin gene-related peptide release from primary afferents.
In the rat and guinea-pig isolated ureter electrical field stimulation of intrinsic nerves (10 Hz for 10 s) produces transient inhibition of evoked (20 mM KCl or 0.1-1 microM neurokinin A) rhythmic contractions by releasing transmitter(s) from peripheral endings of capsaicin-sensitive primary afferents. The C-terminal fragment of human calcitonin gene-related peptide (8-37) blocked the inhibitory effect of electrical field stimulation as well as that produced by exogenous calcitonin gene-related peptide, while leaving unaffected the inhibitory response to isoprenaline. Human calcitonin gene-related peptide (8-37) was devoid of any inhibitory activity of its own but enhanced the amplitude and frequency of KCl-evoked rhythmic contractions in the rat ureter, probably by antagonizing the inhibitory effect of endogenous calcitonin gene-related peptide released by KCl. Omega conotoxin fraction GVIA, a peptide which possesses a potent blocking activity of N-type voltage-sensitive calcium channels, prevented the inhibitory response to electrical stimulation in the guinea-pig ureter, while leaving the response unaffected in the rat ureter. Conotoxin had no effect toward the inhibition produced by exogenous calcitonin gene-related peptide indicating its prejunctional site of action, demonstrated previously in the guinea-pig ureter [Maggi et al. (1990) Neurosci, Lett. 114, 203-206]. Dermorphin, an amphibian peptide with potent agonist activity on mu-type opioid receptors, inhibited the response to electrical stimulation in the guinea-pig ureter but had no effect in the rat ureter.(ABSTRACT TRUNCATED AT 250 WORDS)
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D019004:Galanin; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D015288:Neurokinin A / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014513:Ureter / Q000294:innervation*; D020866:omega-Conotoxin GVIA
D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D010455:Peptides; D010456:Peptides, Cyclic; C058636:calcitonin gene-related peptide (8-37); C030058:dermorphin; D011189:Potassium Chloride; D015288:Neurokinin A; D019004:Galanin; D020866:omega-Conotoxin GVIA; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol