Activities and antagonism of bombesin on urinary smooth muscles.
Substance P (SP), bombesin (BB) and bradykinin (BK) induce dose-dependent contractions of the rat and guinea-pig urinary bladders (RUB, GPUB). The three peptides differ in their affinities and intrinsic activities, BB being the most active both in terms of affinity (pD2 8.33 in the RUB and 8.83 in the GPUB), SP (8.03 and 7.53), BK (7.20 and 7.35), and of intrinsic activity. The myotropic effects of BB and SP are not modified by antagonists of neurotransmitters and autacoids that occur in peripheral organs, but that of BK is reduced in the presence of both the cyclooxygenase and lipoxygenase inhibitors. Undeca- and octapeptide antagonist analogues of SP and SP-(4-11) show similar pA2 values against BB and SP and are inactive against BK: the compound [D-Pro4, Lys6, D-Trp7,9,10, Phe11] SP-(4-11) is however more active (pA2 6.36 in the RUB and 6.18 in the GPUB) against BB than against SP (pA2 5.33 and 5.65 respectively), while it is inactive against BK. These results confirm data from the literature as to the ability of some tachykinin-antagonists to act against BB and shows chemical modifications that can improve the antagonist potency selectively against BB.
J
J
Mizrahi
S
S
Dion
P
P
D'Orléans-Juste
D
D
Regoli
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects
D009842:Oligopeptides; D010455:Peptides; D013373:Substance P; D001285:Atropine; D011433:Propranolol; D001839:Bombesin; D001920:Bradykinin; D008784:Methysergide