Identification of separate bombesin and substance P receptors on isolated muscle cells from canine gallbladder.
Smooth muscle cells were isolated from the dog gallbladder and used to examine whether bombesin-14 and substance P cause direct contraction and whether this effect is mediated by the same or different receptors. Both peptides caused concentration-dependent contraction that was inhibited by two substance P derivatives, [D-Pro2,D-Trp7,9]SP ([PTT]SP) and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP ([APTTL]SP). In nonmuscle cells, these substance P derivatives exhibit preferential antagonism of responses to substance P and bombesin, respectively; accordingly, these properties were used to demonstrate the presence of separate bombesin and substance P receptors. Estimates of the apparent Ki showed that [PTT]SP was 40 times more potent than [APTTL]SP as an antagonist of the response to substance P, whereas [APTTL]SP was 85 times more potent than [PTT]SP as an antagonist of the response to bombesin-14. Estimates of median inhibitory concentration obtained from inhibition curves for the effect of various concentrations of each antagonist on the responses to substance P and bombesin-14 confirmed that [PTT]SP was a preferential antagonist of the response to substance P and [APTTL]SP, a preferential antagonist of the response to bombesin-14. The results demonstrate the presence of separate bombesin and substance P receptors mediating contraction of smooth muscle cells of the dog gallbladder.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001839:Bombesin / Q000378:metabolism; D004285:Dogs; D005704:Gallbladder / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D011377:Proglumide / Q000494:pharmacology; D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011994:Recombinant Proteins; D012984:Software; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism
D010446:Peptide Fragments; D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D013373:Substance P; D009270:Naloxone; D001285:Atropine; C045505:substance P (4-11), Pro(4)-Trp(7,9)-; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-; D011377:Proglumide; D001839:Bombesin