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, Ni 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 Ni 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.
The inhibitory mechanism of the gastric acid secretion by the sympatho-adrenomedullary system was examined by electrical stimulation of the greater splanchnic nerves of urethaneanesthetized rats with gastric fistula. Stimulation of the greater splanchnic nerve or adrenal branch of the splanchnic nerve reduced both vagally stimulated acid secretion and mucosal blood flow (MBF). On the other hand, after cutting the adrenal branch, selective stimulation of the postganglionic splanchnic nerve (SP) reduced the vagally stimulated acid secretion without affecting MBF. These direct inhibitions by SP nerve stimulation were also observed in the bethanechol- and pentagastrin-induced acid secretion, but not in the histamine-induced acid secretion. SP-induced inhibition on the vagally stimulated acid secretion was abolished by phentolamine and yohimbine. On the other hand, SP-induced inhibitions on the bethanechol- and pentagastrin-induced acid secretion were abolished by phentolamine and prazosin. From these observations, gastric sympathetic nerves directly inhibit the gastric acid secretion by activation of adrenergic alpha-1 and -2 adrenoceptors, alpha-2 adrenoceptors on the parasympathetic neurons in the gastric wall, and alpha-1 adrenoceptors on the structures near the parietal cells.