Date of Award
Program or Major
Doctor of Philosophy
Winsor H Watson, III
The biochemical basis underlying the chronotropic and inotropic effects of peptides and amines on the neurogenic heart of the horseshoe crab, Limulus polyphemus, was investigated. This study focused on the role of cyclic nucleotide and phosphatidylinostiol metabolism in specific actions of amines and peptides endogenous to the Limulus nervous system. Biochemical and electrophysiological analyses of amine and peptide actions on specific cellular targets within the neurogenic heart network were performed to characterize the intracellular mechanisms responsible for the excitatory effects of these neuromodulators.
Octopamine and the catecholamines dopamine, norepinephrine and epinephrine utilize the second messenger cyclic AMP at multiple cellular sites to increase the rate and strength of heart contractions. These amines increase burst rate in the cardiac ganglion by a cAMP-dependent mechanism. Amines also increase cardiac muscle contractility and enhance cardiac neuromuscular transmission by a cAMP-dependent process. Cyclic GMP does not appear to be involved in any of the excitatory actions of amines, although it may play a role in cardiac inhibition.
Several proctolin-like and FMRFamide-like peptides are widely distributed in the Limulus CNS and may play a role in the regulation of cardiac output. The peptide proctolin utilizes the phosphatidylinositol second messenger system in its actions on cardiac muscle contractility and excitability. Dopamine may also activate this system, as this amine has several proctolin-like actions on Limulus cardiac muscle. Finally, the FMRFamide-like cardioexcitatory peptide limadrin, like the amines, appears to produce excitation of heart rate by increasing levels of cAMP in the Limulus cardiac ganglion. These results indicate that peptide and amine neuromodulators share several second messenger systems to produce their characteristic responses on the Limulus heartbeat.
Groome, James Richard, "Peptide and amine actions on the neurogenic Limulus heart: Biochemical mechanisms of modulation" (1988). Doctoral Dissertations. 1532.