Abstract
The ability of the muscarinic receptor agonist, carbachol. to inhibit β-adrenergic activation of adenylate cyclase was examined in cardiac membranes from 6-month (young adult) and 24-month (aged) old rats in an effort to assess the effect of aging on adrenergic-cholinergic interactions in the heart. At varying concentrations (0.1–100 μM) of carbachol. GTP plus isoproterenol-stimulated adenylate cyclase activity was inhibited 5–39% in cardiac membranes from 6-month-old rats: this inhibition was statistically significant at all but the lowest concentration (0.1 μM) of carbachol used. In contrast, in cardiac membranes from 24-month-old rats, the inhibition of GTP plus isoproterenol-stimulated adenylate cyclase activity by carbachol was very weak (3–20% with 0.1–100 μM carbachol), and statistically insignificant. The muscarinic receptor antagonist, atropine, blocked the inhibition of GTP plus isoproterenol-stimulated enzyme activity by carbachol showing that the observed inhibitory effect of carbachol was muscarinic receptor dependent. The basal adenylate cyclase activity (which showed no significant age-related difference) was unaffected by carbachol. No significant age-related differences were evident in: (a) the concentration of carbachol required for half-maximal inhibition of GTP plus isoproterenol-stimulated adenylate cyclase activity; (b) the density of muscarinic receptor sites; and (c) their agonist and antagonist binding affinities. The GTP plus isoproterenol-stimulated cyclase activity measured in the absence of carbachol was 70% lower in cardiac membranes from 24-month-old, compared to 6-month-old rats, confirming an age-associated decline in β-adrenergic activation of the cyclase observed in our previous study [ Mech. Ageing Dev., 19: (1982) 127–139]. The above findings suggest an apparent age-related decline in the postsynaptic antiadrenergic action of cholinergic stimulus in the heart; thus, exaggerated cholinertic antagonism of β-adrenergic
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
