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 language | English |
|---|---|
| Pages (from-to) | 3601-3607 |
| Number of pages | 7 |
| Journal | Biochemical Pharmacology |
| Volume | 37 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 1 Oct 1988 |
Cite this
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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 journal › Article › Research › peer-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 -