Local motor responses to bradykinin and bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) in the guinea-pig isolated renal pelvis and ureter.
The local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Santicioli
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P
Del Bianco
E
E
Giuliani
S
S
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000031:analogs & derivatives; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007682:Kidney Pelvis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects* / Q000502:physiology
D009842:Oligopeptides; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D009240:N-Formylmethionine Leucyl-Phenylalanine; C033373:butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine; C065679:icatibant; D015288:Neurokinin A; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin