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Peptide and Amine Actions on the Neurogenic Limulus Heart: Biochemical Mechanisms of Modulation James Richard Groome University of New Hampshire, Durham

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Peptide and Amine Actions on the Neurogenic Limulus Heart: Biochemical Mechanisms of Modulation James Richard Groome University of New Hampshire, Durham University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Spring 1988 Peptide and amine actions on the neurogenic Limulus heart: Biochemical mechanisms of modulation James Richard Groome University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Groome, James Richard, "Peptide and amine actions on the neurogenic Limulus heart: Biochemical mechanisms of modulation" (1988). Doctoral Dissertations. 1532. https://scholars.unh.edu/dissertation/1532 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the original text directly from the copy submitted. Thus, some dissertation copies are in typewriter face, while others may be from a computer printer. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyrighted material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each oversize page is available as one exposure on a standard 35 mm slide or as a 17" x 23" black and white photographic print for an additional charge. Photographs included in the original manuscript have been reproduced xerographically in this copy. 35 mm slides or 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. <91UMAccessing the World's Information since 1938 -I 300 North Zeeb Road. Ann Arbor. Ml 48106*1346 USA Order Number 8816687 Peptide and amine actions on the neurogenicLimulus h ea rt: Biochemical mechanisms of modulation Groome, James Richard, Ph.D. University of New Hampshire, 1988 UMI 300 N. Zeeb Rd. Ann Arbor, MI 48106 PLEASE NOTE: In all cases this material has been filmed in the best possible way from the available copy. Problems encountered with this document have been identified here with a check mark V . 1. Glossy photographs or pages ______ 2. Colored illustrations, paper or print ________ 3. Photographs with dark background ______ 4. Illustrations are poor copy _______ 5. Pages with black marks, not original copy _______ 6. Print shows through as there is text on both sides of page_______ 7. Indistinct, broken or small print on several pages 8. Print exceeds margin requirements_______ 9. Tightly bound copy with print lost in s p in e________ 10. Computer printout pages with indistinct print_______ 11. P a g e (s ) _____________ lacking when material received, and not available from school or author. 12. Page(s) seem to be missing in numbering only as text follows. 13. Two pages num bered . Text follows. 14. Curling and wrinkled pages _ 15. Dissertation contains pages with print at a slant, filmed as received 16. Other________ _________________________________________________ PEPTIDE AND AMINE ACTIONS ON THE NEUROGENIC LIMULUS HEART BIOCHEMICAL MECHANISMS OF MODULATION BY JAM ES R. GROOME B. A. Wake Forest University, 1981 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Z o o lo g y M ay, 1988 This dissertation has been examined and approved. Dissertation Director, Dr. Winsor H. Watson Associate Professor of Zoology, University of New Hampshire Dr. Irwin B. Levitan, Professor of Biochemistry, Brandeis University fr. John W. Sasner, Professor of Zoology, University of New Hampshire Dr. Edward K. Tillinghast, Professor of Zoology, University of New Hampshire Dr. Gordon A. Wyse, P ro f^so r of Zoology University of Massachusetts This dissertation is dedicated to the memory of Tom O'Donohue. ACKNOWLEDGEMENTS I would like to thank the members of my doctoral committee for their help in questions regarding experimental protocol and for reviewing this dissertation. Particular thanks is given to Dr. Winsor Watson for introducing me to invertebrate neurobiology, advising me on research objectives, strategies, and techniques, and for his continuing friendship. I would also like to thank the other members of the Zoology Department at UNH, especially Dr. Charles Walker, the staff at the Friday Harbor Labs of the University of Washington, and the members of the O’Donohue lab at NIH in Bethesda, Maryland, for the generous use of their facilities in this research. Antibodies for peptide assays were generously provided by Tom O'Donohue and Barbara Beltz. Thanks are also extended to my fellow graduate students at UNH, my family and friends, who helped me keep a semblance of perspective throughout the course of my graduate work. Finally, special thanks to Bridget Mansfield, Richard Nero and Al Vetrovs for their patient assistance with all those horseshoe crabs. This research was supported by funding from the following sources: NIH 5-R01-NS19053-03, N.H. Heart Assoc. PGM: Fa440A and 86167, UNH CURF S-277 and S-355. TABLE OF CONTENTS DEDICATION.............................................................................................. iii ACKNOWLEDGEMENTS.............................................................................. iv LIST OF TABLES.......................................................................................... vi LIST OF FIGURES.......................................................................................... vii ABSTRACT..................................................................................................... xi CHAPTER PAGE INTRODUCTION.............................................................................................. 1 I. MECHANISM FOR AMINE ACTIONS ON THE LIMULUS CARDIAC GANGLION...................................................................................................... 42 II. MECHANISM FOR AMINE ACTIONS ON CARDIAC MUSCLE CONTRACTILITY AND ON NEUROMUSCULAR TRANSMISSION IN THE LIMULUS HEART.............................................................................................. 79 III. DISTRIBUTION AND PURIFICATION OF PROCTOLIN-LIKE AND FMRFAMIDE-LIKE PEPTIDES IN THE LIMULUS NERVOUS SYSTEM.... 110 IV. MECHANISMS UNDERLYING ACTIONS OF PROCTOLIN-LIKE AND FMRFAMIDE-LIKE PEPTIDES ON THE LIMULUS HEART................. 149 V. CONCLUSIONS AND FUTURE DIRECTIONS.......................................... 182 LIST OF REFERENCES.................................................................................... 188 APPENDIX - GENERAL METHODOLOGY...................................................... 228 v LIST OF TABLES 1. Physiological and biochemical effects of amines and pharmacological agents on the Limulus cardiac ganglion 50 2. Physiological and biochemical effects of amines and pharmacological agents on Limulus cardiac muscle .................... 85 3. Distribution of immunoreactive proctolin in Limulus ................... 118 4. Distribution of immunoreactive FMRFamide in Limulus ............ 129 5. Effects of proctolin, amines and pharmacological agents on deganglionated cardiac muscle ................................................ 162 6. Effects of FMRFamide-like peptides on cAMP levels and physiology in Limulus cardiac ganglia and cardiac muscle 165 LIST OF FIGURES INTRODUCTION 1. Second messenger systems .......................................................... 13 2. Peptide and amine actions on the Limulus heart network 37 CHAPTER ONE 1. Actions of amines and cyclic nucleotide agents on the isolated Limulus heart ...................................................................... 49 2. Amine action on the isolated cardiac ganglion ............................. 51 3. Amine effects on cyclic nucleotide levels in the cardiac ganglion ....................................................................................... 53 4. Onset and washoff of amine-induced elevation of cAMP in the Limulus cardiac ganglion ............................................ 54 5. Dose-response of amine effects on cyclic nucleotides in the cardiac ganglion ........................................................................... 55 6. Effects of forskolin and IBMX on heartrate .................................... 56 7. Effects of forskolin and IBMX on burst rate in the isolated cardiac ganglion .................................................................... 58 8. Correlation of cardiac ganglion burst rate and cAMP levels .... 59 9. Potentiation of amine-induced increases in heart rate and elevation of cardiac ganglion cAM P ....................................... 62 10. Suppression of amine-induced increases in cardiac ganglion cAMP by phentolamine ...................................................................... 63 11. Amine and pharmacological agent effects on follower neurons in the cardiac ganglion ....................................................... 65 12. Alteration of follower neuron burst parameters by forskolin and IB M X .........................................................................
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