アデノシンおよびムスカリン様受容体を介する心機能抑制性制御機構

抄録

In mammalian cardiac muscle, muscarinic and adenosine receptors serve as inhibitory physiological modulators of myocardial functions. Dual inhibitory regulation of myocardial function via stimulation of these receptors is established through cyclic AMP-dependent and cyclic AMP-independent subcellular processes. The inhibitory signals triggered by agonist binding to the respective receptors are transmitted to the subsequent biochemical, electrophysiological and functional changes through activation of the GTP-binding proteins, N_i and/or N₀, which couple the signal at binding sites to the catalytic subunit of adenylate cyclase in the actions mediated through the cyclic AMP-dependent mechanism, or to potassium channels in those mediated by cyclic AMP-independent processes preferentially exerted in atrial and SA nodal cells. The functional role of polyphosphoinositide breakdown promoted by muscarinic receptor activation in myocardium has not been elucidated. IAP (islet-activating protein, pertussis toxin) is capable of uncoupling the receptor stimulation to activation of N_i and/or N₀, thus resulting in the inhibtion of negative inotropic and chronotropic responses to muscarinic receptor agonists, and to adenosine and its derivatives such as N⁶-phenylisopropyladenosine and N⁶-methyladenosine. Both the cyclic AMP-dependent and cyclic AMP-independent inhibitory mechanisms are susceptible to IAP.