TABLE 4

cAMP and CRE-SPAP gene transcription responses to β 2-agonists, partial agonists, and β -blockers after pre-incubation with PTX (100 ng/ml for 24 h)

No CRE-SPAP responses to timolol, bisoprolol, metoprolol, or sotalol were seen in either the absence or after incubation with PTX.

Log EC50 Log EC50 in presence of PTX Emax (response without PTX) n
%
cAMP Accumulation Agonists
Labetolol −8.04 ± 0.06 −7.93 ± 0.16 94.1 ± 3.9 3
Alprenolol −9.07 ± 0.09 −9.05 ± 0.18 96.4 ± 5.3 3
Inverse agonists ICI 118551 −8.85 ± 0.08 −8.91 ± 0.06 98.8 ± 1.8 5
Propranolol (±)-Propranolol −9.14 ± 0.10 −9.00 ± 0.14 95.1 ± 2.2 4
CRE-SPAP Production Agonists
Isoprenaline −8.20 ± 0.16 −8.33 ± 0.18 99.0 ± 4.4 9
Salbutamol −8.62 ± 0.04 −8.63 ± 0.12 102.5 ± 3.6 6
Salmeterol −10.52 ± 0.08 −10.57 ± 0.08 99.0 ± 4.8 3
CGP 12177 −9.53 ± 0.05 −9.70 ± 0.06 102.0 ± 5.7 3
Labetolol −8.82 ± 0.05 −8.72 ± 0.05 101.1 ± 0.8 3
Acebutolol −6.39 ± 0.09 −6.38 ± 0.06 108.2 ± 8.6 3
Pindolol −9.25 ± 0.02 −9.31 ± 0.02 101.4 ± 5.9 3
Alprenolol −9.49 ± 0.03 −9.56 ± 0.14 109.0 ± 2.8 3
Inverse agonists ICI 118551a −9.52 ± 0.047 −9.47 ± 0.08 109.2 ± 8.2 3
Propranolol (±)-Propranolol −9.58 ± 0.12 −9.35 ± 0.08 118.4 ± 15.1 4
  • a To maximize the chance of seeing any change to this small inverse agonist response, 100 nM forskolin was added to all wells (both those with and without PTX incubation) to increase the `basal' adenylyl cyclase activity. Under these conditions, in the absence of PTX, ICI 118551 reduced basal to 54.9 ± 2.0% of untreated (n = 3).