Pmg. Neuro-Psychopharmacol. (j. Bial. Psychiat. 1986, Vol. 10, PP. 323-353 0278-5846186 $0.00 + 50 Printed in Great Britsin. All rights reserved. Copyright @ 1986 Pergamon Journals Ltd. zyxwvut THE CYCLIC AMP SECOND MESSENGER SYSTEM IN MAN: THE EFFECTS OF HEREDITY, HORMONES, DRUGS, ALUMINUM, AGE AND DISEASE ON SIGNAL ~LIFICATION RICHARD P. EBSTEIN, GERALDOPPENREIMl, BONNIES. EBSTEIN, EAMIRAMIRI andJKIiANANSTESsMAN Departmaht of Geriatric Research, EzrathRashimHospital, Jerusalan, and 1Alzheimer's DiseaseTreatment and Study Program, Department of Psychiatry, ShaareZedekMedical Center,Jerusalem, Israel (Final form,February 1986) Contents 1. 2. 2.1 2.2 2.3 2.4 2.4.1 2.4.2 2.4.3 2.4.4 2.5 3. 3.1 3.2 3.3 Abstract Introduction 324 The Effectof VariOUS Vectorsan Adenylate Cyclase Activity in Man 325 The Role of Heredity: Twin Studies 327 The Actionof Ehdogenous Gatecholamines on beta-Adrenergic Receptors 327 329 The Effectof Endogenous Steroid Hormones on CyclicAMP Accumulation in Lymphocytes: ChangesDuringthe&+nstrual zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC Cycle 329 HumahAdenylate Cyclaseas a Targetfor Therapeutic Drug Action: 329 Propranolol 329 Beta-adrenergic Agonists miiodothyrone 329 Lithim 330 330 BY Aluminum:Is Adenylate Cyclasea Site of Possible Aluminum Toxicityin Alzheimer's 331 Disease? 332 EnviromentalSources of Al 332 AlamdAlzheimer'sDisease 332 Al activation of HumanAdenylate Cyclase 333 4. Changesin Adenylate GyclaseActivityin Normal zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR Human Aging 334 4.1 4.2 4.2.1 4.2.2 5. Studies With Lymphocytes Peripheral Perfusion Studies With Salbutamol and Glucagon Salbutmol Glucagon Cyclic AMP Signal Amplification Abnormalities in Human Disease Psetiohypopwathyroidism Type I Dowh'ssyndrcm Affective Disorders &% Fibrosis Alzheimer's Disease 334 337 337 339 Pathologyand Alzheimer's 340 340 341 341 3'12 342 343 5.1 5.2 5.3 5.4 5.5 5.6 5.6.1 6. Self-regulation FutureProspects and Strategies in Research on Human SecondMessenger systems Acknowledgements References 345 347 349 349 323