Persistent β-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea

Peter Molenaar, Fraser Russell, Joseph Pitha, Roger Summers

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

The actions of alkylating pindolol (N8-bromoacetyl-N1-3′-(4-indolyloxy)-2′-hydroxypropyl-[z]-1,8-diamino-p-menthane; BIM) have been examined on β-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (≥0.1μM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The "apparent" pA2; value for BIM was 9.23 ± 0.20 (slope = 0.98 ± 0.20). Changes in the maximal density of β-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I]-cyanopindolol. BIM (0.1, 1.0 and 10 μM) produced 14, 23 and 41% reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The "apparent" KD, value of [125I]-BIM at β-adrenoceptor binding sites was 85.7 ± 57.9 pM.

Original languageEnglish
Pages (from-to)3601-3607
Number of pages7
JournalBiochemical Pharmacology
Volume37
Issue number19
DOIs
Publication statusPublished - 1 Oct 1988

Cite this

Molenaar, Peter ; Russell, Fraser ; Pitha, Joseph ; Summers, Roger. / Persistent β-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea. In: Biochemical Pharmacology. 1988 ; Vol. 37, No. 19. pp. 3601-3607.
@article{8789d20d918a477f90ba29348a0ee39c,
title = "Persistent β-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea",
abstract = "The actions of alkylating pindolol (N8-bromoacetyl-N1-3′-(4-indolyloxy)-2′-hydroxypropyl-[z]-1,8-diamino-p-menthane; BIM) have been examined on β-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (≥0.1μM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The {"}apparent{"} pA2; value for BIM was 9.23 ± 0.20 (slope = 0.98 ± 0.20). Changes in the maximal density of β-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I]-cyanopindolol. BIM (0.1, 1.0 and 10 μM) produced 14, 23 and 41{\%} reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The {"}apparent{"} KD, value of [125I]-BIM at β-adrenoceptor binding sites was 85.7 ± 57.9 pM.",
author = "Peter Molenaar and Fraser Russell and Joseph Pitha and Roger Summers",
year = "1988",
month = "10",
day = "1",
doi = "10.1016/0006-2952(88)90390-5",
language = "English",
volume = "37",
pages = "3601--3607",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier",
number = "19",

}

Persistent β-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea. / Molenaar, Peter; Russell, Fraser; Pitha, Joseph; Summers, Roger.

In: Biochemical Pharmacology, Vol. 37, No. 19, 01.10.1988, p. 3601-3607.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Persistent β-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea

AU - Molenaar, Peter

AU - Russell, Fraser

AU - Pitha, Joseph

AU - Summers, Roger

PY - 1988/10/1

Y1 - 1988/10/1

N2 - The actions of alkylating pindolol (N8-bromoacetyl-N1-3′-(4-indolyloxy)-2′-hydroxypropyl-[z]-1,8-diamino-p-menthane; BIM) have been examined on β-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (≥0.1μM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The "apparent" pA2; value for BIM was 9.23 ± 0.20 (slope = 0.98 ± 0.20). Changes in the maximal density of β-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I]-cyanopindolol. BIM (0.1, 1.0 and 10 μM) produced 14, 23 and 41% reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The "apparent" KD, value of [125I]-BIM at β-adrenoceptor binding sites was 85.7 ± 57.9 pM.

AB - The actions of alkylating pindolol (N8-bromoacetyl-N1-3′-(4-indolyloxy)-2′-hydroxypropyl-[z]-1,8-diamino-p-menthane; BIM) have been examined on β-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (≥0.1μM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The "apparent" pA2; value for BIM was 9.23 ± 0.20 (slope = 0.98 ± 0.20). Changes in the maximal density of β-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I]-cyanopindolol. BIM (0.1, 1.0 and 10 μM) produced 14, 23 and 41% reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The "apparent" KD, value of [125I]-BIM at β-adrenoceptor binding sites was 85.7 ± 57.9 pM.

UR - http://www.scopus.com/inward/record.url?scp=0023787001&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(88)90390-5

DO - 10.1016/0006-2952(88)90390-5

M3 - Article

VL - 37

SP - 3601

EP - 3607

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 19

ER -