Adrenergic and calcium modulation of the heart in stress: From molecular biology to function

Figures & data

Table I.  Pharmacological characteristics of individual adrenoreceptor subtypes and coupling to G proteins with subsequent activation of second messengers.

Receptor	Adrenaline	Noradrenaline	G protein	Second messenger
α1A	0.3	1.2–2.8	Gq/G11	IP3/Ca^2 + ; DAG
α1B	6	10	Gq/G11	IP3/Ca^2 + ; DAG
α1D	0.016	0.012	Gq/G11	IP3/Ca^2 + ; DAG
α2A	8.3–5.6*	8.4–5.6*	Gi/Go	↓ Cyclic AMP
α2B	6.2–5.2*	9.1–5.6*	Gi/Go	↓ Cyclic AMP
α2C	6.2–5.8*	8.7–5.9*	Gi/Go	↓ Cyclic AMP
β1	1.0 2.7#	0.5 0.8#	Gs	↑ Cyclic AMP
β2	0.9–0.7 2.2#	10–6 (9.7) 36#	Gs	↑ Cyclic AMP
β3	4.7–3.9* 49#	3.8–5.3* 6.3#	Gi Gs	↓ Cyclic AMP ↑ Cyclic AMP

Pharmacological characteristics of adrenoceptor subtypes are expressed as EC50 (expressed as μmol l − 1) or pKi (*) or K_AC (activation constant of AC stimulation; expressed as nmol.l − 1)#. Data are given as in Bylund et al. (1994), Chen et al. (1994) (EC50), IUPHAR receptor database (http://www.iuphar-db.org/GPCR/; Ki), and Skeberdis (2004) (K_AC). Coupling to G proteins and second messenger system(s) are also shown. Please note that the coupling of α₁-adrenoceptors with PLD (α_1A>α_1B>α_1D) was not included in the table as the precise mechanism of activation is not known yet; all three subtypes are able to activate PLD, but the mechanisms may differ in different cell types.

Figure 1 Signaling cascades of individual types of adrenergic receptors. AC, adenylate cyclase; DAG, diacylglycerol; DHPR, dihydropyridine receptor, G_s; G_i, Gq_/11, G proteins type s, i and q; IP₃, inositol 1,4,5-trisphosphate; IP₃R, IP₃ receptor; NCX, sodium calcium exchanger; PKA, protein kinase A; PKB, protein kinase B; PKC, protein kinase C; PLC, phospholipase C; PIP2, phosphatidylinositol 4,5-diphosphate; RyR, ryanodine receptor; PLB, phospholamban; SERCA, sarcoplasmic reticulum calcium ATPase; CaMKII, calmodulin-dependent kinase II; PI3K, phosphatidyl inositol 3-kinase.

Figure 2 Effect of c-fos knockout on the IP₃R1 mRNA in the cardiac left atria in control conditions (A) and after a single immobilization stress (B; IMO). Each column represents an average of three animals. Statistical significance *** represents p < 0.0001.

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