Activation of opioid receptors dramatically decreases the degree of ischemic damage in rat myocardium. This cardioprotective phenomenon
may be mediated by a protein kinase C (PKC)-dependent modification of myofibrillar proteins, leading to reduced ATP utilization by the
myofilaments.
We tested this hypothesis by correlating post-ischemic contractile recovery and myofibrillar actomyosin Mg2+ATPase activity in isolated rat hearts. Pre-ischemic treatment with the k-opioid receptor agonist U50,488 (U50, 1 mM) improved post-ischemic left ventricular developed pressure (LVDP) by 35% over control hearts. Non-ischemic and post-ischemic myofibrillar actomyosin Mg2+ATPase activity were reduced by 20% in U50 treated hearts, as compared to control hearts. Decreased myofilament ATP consumption with cardioprotective agents was also demonstrated in isolated ventricular myocytes. The PKC-activator phorbol 12-myristate acid (1 mM) and U50 both slowed the maximal velocity of unloaded shortening by 15% to 25%. Exogenous PKC-e mimicked the U50-dependent reduction in myofibrillar actomyosin Mg2+ATPase activity. ATP levels were 173% higher in non-ischemic hearts treated with U50, and 107% higher at the end of ischemia, compared to control hearts, which is consistent with decreased ATP utilization by the myofilaments. The improved post-ischemic LVDP and U50-dependent decrease in actomyosin Mg2+ATPase activity were blocked by the PKC inhibitors chelerythrine chloride (2 mM) and bisindolylmaleimide (100 nm). Confocal microscopy and Western blot analysis of isolated ventricular myocytes showed translocation of PKC-e and -d to the myofibrillar fraction with U50 treatment. U50 increased myofibrillar Ca2+-independent PKC activity. U50 treatment resulted in an increased phosphorylation of troponin I and C-protein in isolated ventricular myocytes. Chelerythrine chloride attenuated the U50-dependent increases in troponin I and C-protein phosphorylation.
These results indicate that k-opioid receptor dependent cardioprotection is mediated through a PKC-dependent modification of the myofilaments which slows the utilization of ATP by the actomyosin ATPase.
","abstract_html":"<p>Activation of opioid receptors dramatically decreases the degree of ischemic damage in rat myocardium. This cardioprotective phenomenon <br />may be mediated by a protein kinase C (PKC)-dependent modification of myofibrillar proteins, leading to reduced ATP utilization by the <br />myofilaments.</p> <p> We tested this hypothesis by correlating post-ischemic contractile recovery and myofibrillar actomyosin Mg2+ATPase activity in isolated rat hearts. Pre-ischemic treatment with the k-opioid receptor agonist U50,488 (U50, 1 mM) improved post-ischemic left ventricular developed pressure (LVDP) by 35% over control hearts. Non-ischemic and post-ischemic myofibrillar actomyosin Mg2+ATPase activity were reduced by 20% in U50 treated hearts, as compared to control hearts. Decreased myofilament ATP consumption with cardioprotective agents was also demonstrated in isolated ventricular myocytes. The PKC-activator phorbol 12-myristate acid (1 mM) and U50 both slowed the maximal velocity of unloaded shortening by 15% to 25%. Exogenous PKC-e mimicked the U50-dependent reduction in myofibrillar actomyosin Mg2+ATPase activity. ATP levels were 173% higher in non-ischemic hearts treated with U50, and 107% higher at the end of ischemia, compared to control hearts, which is consistent with decreased ATP utilization by the myofilaments. The improved post-ischemic LVDP and U50-dependent decrease in actomyosin Mg2+ATPase activity were blocked by the PKC inhibitors chelerythrine chloride (2 mM) and bisindolylmaleimide (100 nm). Confocal microscopy and Western blot analysis of isolated ventricular myocytes showed translocation of PKC-e and -d to the myofibrillar fraction with U50 treatment. U50 increased myofibrillar Ca2+-independent PKC activity. U50 treatment resulted in an increased phosphorylation of troponin I and C-protein in isolated ventricular myocytes. Chelerythrine chloride attenuated the U50-dependent increases in troponin I and C-protein phosphorylation.</p> <p> These results indicate that k-opioid receptor dependent cardioprotection is mediated through a PKC-dependent modification of the myofilaments which slows the utilization of ATP by the actomyosin ATPase.</p>","abstract_has_math":false,"creators":["Pyle, William Glen"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Polly A. Hofmann, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1999,"date_issued":"1999-12-01T08:00:00Z","date_published":"1999-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:17Z","subjects":["opioid","cardioprotection","preconditioning","heart","actin-myosin cycling","actomyosin MgATPase","protein kinase C","ATP","myofilaments","rats","Medical Physiology","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/209","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Polly A. Hofmann, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Pyle, William Glen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-10T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["opioid","cardioprotection","preconditioning","heart","actin-myosin cycling","actomyosin MgATPase","protein kinase C","ATP","myofilaments","rats","Medical Physiology","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/209"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Activation of opioid receptors dramatically decreases the degree of ischemic damage in rat myocardium. This cardioprotective phenomenon
may be mediated by a protein kinase C (PKC)-dependent modification of myofibrillar proteins, leading to reduced ATP utilization by the
myofilaments.
We tested this hypothesis by correlating post-ischemic contractile recovery and myofibrillar actomyosin Mg2+ATPase activity in isolated rat hearts. Pre-ischemic treatment with the k-opioid receptor agonist U50,488 (U50, 1 mM) improved post-ischemic left ventricular developed pressure (LVDP) by 35% over control hearts. Non-ischemic and post-ischemic myofibrillar actomyosin Mg2+ATPase activity were reduced by 20% in U50 treated hearts, as compared to control hearts. Decreased myofilament ATP consumption with cardioprotective agents was also demonstrated in isolated ventricular myocytes. The PKC-activator phorbol 12-myristate acid (1 mM) and U50 both slowed the maximal velocity of unloaded shortening by 15% to 25%. Exogenous PKC-e mimicked the U50-dependent reduction in myofibrillar actomyosin Mg2+ATPase activity. ATP levels were 173% higher in non-ischemic hearts treated with U50, and 107% higher at the end of ischemia, compared to control hearts, which is consistent with decreased ATP utilization by the myofilaments. The improved post-ischemic LVDP and U50-dependent decrease in actomyosin Mg2+ATPase activity were blocked by the PKC inhibitors chelerythrine chloride (2 mM) and bisindolylmaleimide (100 nm). Confocal microscopy and Western blot analysis of isolated ventricular myocytes showed translocation of PKC-e and -d to the myofibrillar fraction with U50 treatment. U50 increased myofibrillar Ca2+-independent PKC activity. U50 treatment resulted in an increased phosphorylation of troponin I and C-protein in isolated ventricular myocytes. Chelerythrine chloride attenuated the U50-dependent increases in troponin I and C-protein phosphorylation.
These results indicate that k-opioid receptor dependent cardioprotection is mediated through a PKC-dependent modification of the myofilaments which slows the utilization of ATP by the actomyosin ATPase.
"]},{"key":"dc:title","label":"Title","values":["k-Opioid Receptor Dependent Cardioprotection in the Rat"]}]}],"canonical_facts":{"dc:contributor":["Polly A. Hofmann, Ph.D."],"dc:creator":["Pyle, William Glen"],"dc:date.available":["2016-06-10T07:00:00Z"],"dc:description.abstract":["Activation of opioid receptors dramatically decreases the degree of ischemic damage in rat myocardium. This cardioprotective phenomenon
may be mediated by a protein kinase C (PKC)-dependent modification of myofibrillar proteins, leading to reduced ATP utilization by the
myofilaments.
We tested this hypothesis by correlating post-ischemic contractile recovery and myofibrillar actomyosin Mg2+ATPase activity in isolated rat hearts. Pre-ischemic treatment with the k-opioid receptor agonist U50,488 (U50, 1 mM) improved post-ischemic left ventricular developed pressure (LVDP) by 35% over control hearts. Non-ischemic and post-ischemic myofibrillar actomyosin Mg2+ATPase activity were reduced by 20% in U50 treated hearts, as compared to control hearts. Decreased myofilament ATP consumption with cardioprotective agents was also demonstrated in isolated ventricular myocytes. The PKC-activator phorbol 12-myristate acid (1 mM) and U50 both slowed the maximal velocity of unloaded shortening by 15% to 25%. Exogenous PKC-e mimicked the U50-dependent reduction in myofibrillar actomyosin Mg2+ATPase activity. ATP levels were 173% higher in non-ischemic hearts treated with U50, and 107% higher at the end of ischemia, compared to control hearts, which is consistent with decreased ATP utilization by the myofilaments. The improved post-ischemic LVDP and U50-dependent decrease in actomyosin Mg2+ATPase activity were blocked by the PKC inhibitors chelerythrine chloride (2 mM) and bisindolylmaleimide (100 nm). Confocal microscopy and Western blot analysis of isolated ventricular myocytes showed translocation of PKC-e and -d to the myofibrillar fraction with U50 treatment. U50 increased myofibrillar Ca2+-independent PKC activity. U50 treatment resulted in an increased phosphorylation of troponin I and C-protein in isolated ventricular myocytes. Chelerythrine chloride attenuated the U50-dependent increases in troponin I and C-protein phosphorylation.
These results indicate that k-opioid receptor dependent cardioprotection is mediated through a PKC-dependent modification of the myofilaments which slows the utilization of ATP by the actomyosin ATPase.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/209"],"dc:subject":["opioid","cardioprotection","preconditioning","heart","actin-myosin cycling","actomyosin MgATPase","protein kinase C","ATP","myofilaments","rats","Medical Physiology","Medical Sciences","Medicine and Health Sciences"],"dc:title":["k-Opioid Receptor Dependent Cardioprotection in the Rat"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:17Z"}