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Characterization of bradykinin receptors in guinea pig gall bladder.
J Pharmacol Exp Ther. 1993 Sep; 266(3):1291-9.JP

Abstract

Specific binding of [3H]bradykinin (BK) to guinea pig gall bladder (GPGB) membranes was protein dependent, rapid (Kon = 0.067 min-1) with high affinity (Kd = 0.45 +/- 0.02; n = 3), saturable (Bmax = 546 +/- 56 fmol/mg of protein) and showed no cooperativity (nH = 1.19 +/- 0.08). A BK B2 receptor type was indicated by the rank order of potency for inhibition of binding by B2 antagonists, [(D)Arg-[Hyp3,Thi5,(D)Tic7-Oic8]-bradykinin (HOE140) > (D)Arg-[Hyp3,(D)HypE(transpropyl)7-Oic8]-bradykinin (NPC17731) > (D)Arg-[Hyp3,Thi5, (D)Tic7-Tic8]-bradykinin (NPC16731) > (D)Arg-[Hyp3,(D)Phe7]-bradykinin (NPC567)] and agonists (BK = kallidin = Tyr(Me)8-BK > Tyr8-BK,> Hyp4-kallidin) as well as inactivity of the B1 agonist des(Arg9)-BK. Nonhydrolyzable GTP analogs (GTP-gamma-S and guanylyl-5'-imido-diphosphate) produced 80% inhibition of specific binding suggesting receptor coupling to guanine nucleotide-binding proteins. BK increased polyphosphoinositide hydrolysis in chopped GPGB in a concentration-dependent manner (0.01-300 microM; EC50 = 414 +/- 171 nM; n = 3-9 tissues/concentration). HOE140 and NPC16731, inhibited BK-induced polyphosphoinositide hydrolysis but only the latter appeared competitive (pKb 8.09 +/- 0.19, n = 3). U73122, an inhibitor of phospholipase C pathway, also inhibited BK-induced turnover in GPGB (IC50 = 46.9 +/- 17.3 nM). BK produced a concentration-related contraction of isolated strips of GPGB. Indomethacin significantly decreased both the potency and efficacy of BK whereas thiorphan, a neutral endopeptidase inhibitor, and/or captopril, an angiotensin-converting enzyme inhibitor, enhanced potency.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology, Zeneca Pharmaceuticals Group, Business Unit of ZENECA Inc., Wilmington, Delaware.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8396632

Citation

Falcone, R C., et al. "Characterization of Bradykinin Receptors in Guinea Pig Gall Bladder." The Journal of Pharmacology and Experimental Therapeutics, vol. 266, no. 3, 1993, pp. 1291-9.
Falcone RC, Hubbs SJ, Vanderloo JD, et al. Characterization of bradykinin receptors in guinea pig gall bladder. J Pharmacol Exp Ther. 1993;266(3):1291-9.
Falcone, R. C., Hubbs, S. J., Vanderloo, J. D., Prosser, J. C., Little, J., Gomes, B., Aharony, D., & Krell, R. D. (1993). Characterization of bradykinin receptors in guinea pig gall bladder. The Journal of Pharmacology and Experimental Therapeutics, 266(3), 1291-9.
Falcone RC, et al. Characterization of Bradykinin Receptors in Guinea Pig Gall Bladder. J Pharmacol Exp Ther. 1993;266(3):1291-9. PubMed PMID: 8396632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of bradykinin receptors in guinea pig gall bladder. AU - Falcone,R C, AU - Hubbs,S J, AU - Vanderloo,J D, AU - Prosser,J C, AU - Little,J, AU - Gomes,B, AU - Aharony,D, AU - Krell,R D, PY - 1993/9/1/pubmed PY - 1993/9/1/medline PY - 1993/9/1/entrez SP - 1291 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 266 IS - 3 N2 - Specific binding of [3H]bradykinin (BK) to guinea pig gall bladder (GPGB) membranes was protein dependent, rapid (Kon = 0.067 min-1) with high affinity (Kd = 0.45 +/- 0.02; n = 3), saturable (Bmax = 546 +/- 56 fmol/mg of protein) and showed no cooperativity (nH = 1.19 +/- 0.08). A BK B2 receptor type was indicated by the rank order of potency for inhibition of binding by B2 antagonists, [(D)Arg-[Hyp3,Thi5,(D)Tic7-Oic8]-bradykinin (HOE140) > (D)Arg-[Hyp3,(D)HypE(transpropyl)7-Oic8]-bradykinin (NPC17731) > (D)Arg-[Hyp3,Thi5, (D)Tic7-Tic8]-bradykinin (NPC16731) > (D)Arg-[Hyp3,(D)Phe7]-bradykinin (NPC567)] and agonists (BK = kallidin = Tyr(Me)8-BK > Tyr8-BK,> Hyp4-kallidin) as well as inactivity of the B1 agonist des(Arg9)-BK. Nonhydrolyzable GTP analogs (GTP-gamma-S and guanylyl-5'-imido-diphosphate) produced 80% inhibition of specific binding suggesting receptor coupling to guanine nucleotide-binding proteins. BK increased polyphosphoinositide hydrolysis in chopped GPGB in a concentration-dependent manner (0.01-300 microM; EC50 = 414 +/- 171 nM; n = 3-9 tissues/concentration). HOE140 and NPC16731, inhibited BK-induced polyphosphoinositide hydrolysis but only the latter appeared competitive (pKb 8.09 +/- 0.19, n = 3). U73122, an inhibitor of phospholipase C pathway, also inhibited BK-induced turnover in GPGB (IC50 = 46.9 +/- 17.3 nM). BK produced a concentration-related contraction of isolated strips of GPGB. Indomethacin significantly decreased both the potency and efficacy of BK whereas thiorphan, a neutral endopeptidase inhibitor, and/or captopril, an angiotensin-converting enzyme inhibitor, enhanced potency.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8396632/Characterization_of_bradykinin_receptors_in_guinea_pig_gall_bladder_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8396632 DB - PRIME DP - Unbound Medicine ER -