Figure 4.

Ex vivo biological (panel A) and in silico simulated (panel B) models showing corrected E/c curves of an agonist with a short half-life, in the absence and presence of an agonist transport inhibitor, acting in systems with unaffected (filled symbols) and reduced (open symbols) receptor number (while symbols of the built-in in silico control curves labelled as “unbiased” are simply x and asterisk). The x-axis denotes the common logarithm of the molar concentration of agonists (in the bathing medium), and the y-axis indicates the effect. The dotted lines between symbols only connect them, while the dotted lines without symbols represent the Hill equation fitted to data of the control adenosine E/c curve (panel A) and the simple unbiased E/c curve of agonist A generated upon naïve receptor population (panel B). Ado: adenosine; NBTI: a treatment with S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine; FSCPX: a prior treatment with 8-cyclopentyl-N³-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N¹-propylxanthine; A: agonist A (simulating adenosine); TI: a treatment with an inhibitor of agonist A transport (simulating the presence of NBTI); IA: a prior treatment with an irreversible antagonist (simulating an FSCPX pretreatment); unbiased: unbiased E/c curves of agonist A (control functions for the corresponding corrected E/c curves); corrected: E/c curves corrected with our method; CF: contractile force. Data of panel A are redrawn from [31].