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November 16, 1970, Vol 214, No. 7 >
ARTICLE | November 16, 1970

On the Biological Role of Cyclic AMP FREE

Earl W. Sutherland, MD
[+] Author Affiliations

Presented as a 1970 Albert Lasker Basic Medical Research Award Lecture, New York, Nov 12,1970.

Reprint requests to Vanderbilt University School of Medicine, Nashville, Tenn 37203.


JAMA. 1970;214(7):1281-1288. doi:10.1001/jama.1970.03180070047009
Text Size: A A A
Published online
Article
References

Before discussing the role of cyclicadenylate, or adenosine 3′,5′-monophosphate (cyclic AMP) in biology, I would like to make a few brief remarks about another subject, the role of the basic scientist in medicine. I would like to hope that this and the subject that I have been asked to write about are not completely unrelated.

I bring this other subject up for two main reasons. First, I am myself optimistic about what the scientist can offer to the world, and especially to medicine. But second, I find others, ranging from beginning medical students to high government officials, who are not so optimistic. I am not overly concerned about our medical students, for the young have always been short on historical perspective and long on idealism. They sense, quite rightly in my view, that American medicine has fallen short of its earlier promise, and they are impatient to do something about

REFERENCES

1 +
Makman RS, Sutherland EW:  Adenosine 3′, 5′-phosphate in Escherichia coli . J Biol Chem 240:1309-1314, 1965;.
2 +
Pastan I, Perlman R:  Cyclic adenosine monophosphate in bacteria . Science 169:339-344, 1970;.
3 +
Sutherland EW, Butcher RW, Robison GA, et al:  The role of adenosine 3′, 5′-monophosphate in hormone action , in Karlson P (ed): Wirkungsmechanismen der Hormone . Berlin, Springer-Verlag, 1967;, pp 1-32.
4 +
Sutherland EW, Robison GA, Butcher RW:  Some aspects of the biological role of adenosine 3′, 5′-monophosphate (cyclic AMP) . Circulation 37:279-306, 1968;.
5 +
Sutherland EW, Robison GA:  The role of cyclic AMP in the control of carbohydrate metabolism . Diabetes 18:797-819, 1969;.
6 +
Robison GA, Butcher RW, Sutherland EW:  On the relation of hormone receptors to adenyl cyclase , in Danielli JF, Moran JF, Triggle DJ, Fundamental Concepts in Drug-Receptor Interactions . London, Academic Press, 1969;, pp 59-91.
7 +
Davoren PR, Sutherland EW:  The cellular location of adenyl cyclase in the pigeon erythrocyte . J Biol Chem 238:3016-3023, 1963;.
8 +
Øye I, Sutherland EW:  Effect of epinephrine and other agents on adenyl cyclase in cell membrane of avian erythrocytes . Biochim Biophy Acta 127:347-354, 1966;.
9 +
Rosen OM, Rosen SM:  Properties of an adenyl cyclase partially purified from frog erythrocytes . Arch Biochem 131:449-456, 1969;.
10 +
Pohl SL, Birnbaumer L, Rodbell M:  Glucagon-sensitive adenyl cyclase in plasma membrane of hepatic parenchymal cell . Science 164:566-567, 1969;.
11 +
Lefkowitz RJ, Roth J, Pricer W, et al:  ACTH receptors in the adrenal: Specific binding of ACTH-125 I and its relation to adenyl cyclase . Proc Nat Acad Sci USA 65:745-752, 1970;.
12 +
Rabinowitz M, Desalles L, Meisler J, et al:  Distribution of adenyl-cyclase activity in rabbit skeletal muscle fractions . Biochim Biophys Acta 97:29-36, 1965;.
13 +
Entman ML, Levey GS, Epstein SE:  Demonstration of adenyl cyclase activity in canine cardiac sarcoplasmic reticulum . Biochem Biophys Res Commun 35:729-733, 1969;.
14 +
Butcher RW, Sutherland EW:  Purification and properties of cyclic 3′, 5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′, 5′-phosphate in human urine . J Biol Chem 237:1244-1250, 1962;.
15 +
Cheung WY:  Properties of cyclic 3′, 5′-nucleotide phosphodiesterase from rat brain . Biochemistry 6:1079-1087, 1967;.
16 +
Moore PF:  Effects of diazoxide and benzothiadiazine diuretics upon phosphodiesterase . Ann NY Acad Sci 150:256-260, 1968;.
17 +
Honda F, Imamura J:  Inhibition of cyclic 3′, 5′-nucleotide phosphodiesterase by phenothiazine and reserpine derivatives . Biochim Biophys Acta 161:267-269, 1968;.
18 +
O'Dea RF, Haddox MK, Goldberg ND:  Kinetic analysis of a soluble rat brain cyclic nucleotide phosphodiesterase , abstracted. Fed Proc 29:473, 1970;.
19 +
Robison GA, Sutherland EW:  Sympathin E, sympathin I, and the intracellular level of cyclic AMP . Circ Res 27 ( (suppl 1) ): 147-161, 1970;.
20 +
Butcher RW, Baird CE:  Effects of prostaglandins on adenosine 3′, 5′-monophosphate levels in fat and other tissues . J Biol Chem 243:1713-1717, 1968;.
21 +
Abe K, Robison GA, Liddle GW, et al:  Role of cyclic AMP in mediating effects of MSH, norepinephrine, and melatonin on frog skin color . Endocrinology 85:674-682, 1969;.
22 +
Jefferson LS, Exton JH, Butcher RW, et al:  Role of adenosine 3′, 5′-monophosphate in the effects of insulin and antiinsulin serum on liver metabolism . J Biol Chem 243:1031-1038, 1968;.
23 +
Butcher RW, Baird CE, Sutherland EW:  Effects of lipolytic and antilipolytic substances on adenosine 3′, 5′-monophosphate levels in isolated fat cells . J Biol Chem 243:1705-1712, 1968;.
24 +
Chesney TM, Schofield JG:  Studies on the secretion of pancreatic glucagon . Diabetes 18:627-632, 1969;.
25 +
Friedmann N, Exton JH, Park CR:  Interaction of adrenal steroids and glucagon on gluconeogenesis in perfused rat liver . Biochem Biophys Res Commun 29: 113-119, 1967;.
26 +
Moskowitz J, Fain JN:  Stimulation by growth hormone and dexamethasone of labeled cyclic adenosine 3′, 5′-monophosphate accumulation by white fat cells . J Biol Chem 245:1101-1107, 1970;.
27 +
Breckenridge BM:  Cyclic AMP and drug action . Ann Rev Pharmacol 10:19-34, 1970;.
28 +
Walsh DA, Perkins JP, Krebs EG:  An adenosine 3′, 5′-monophosphate-dependent protein kinase from rabbit skeletal muscle . J Biol Chem 243:3763-3765, 1968;.
29 +
Kuo JF, Greengard P:  Widespread occurrence of adenosine 3′, 5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom . Proc Nat Acad Sci 64:1349-1355, 1969;.
30 +
Gill GN, Garren LD:  A cyclic 3′, 5′-adenosine monophosphate dependent protein kinase from adrenal cortex: Comparison with a cyclic AMP binding protein . Biochem Biophys Res Commun 39:335-343, 1970;.
31 +
Somlyo AV, Haeusler G, Somlyo AP:  Cyclic adenosine monophosphate: Potassium-dependent action on vascular smooth muscle membrane potential . Science 169:490-491, 1970;.
32 +
Robison GA, Butcher RW, Sutherland EW: Cyclic AMP . New York, Academic Press Inc, to be published.
33 +
Lundholm L, Rall TW, Vamos N:  Influence of K-ions and adrenaline on the adnosine 3′, 5′-monophosphate content in rat diaphragm . Acta Physiol Scand 70:127-128, 1967;.
34 +
Namm DH, Mayer SE, Maltbie M:  Role of potassium and calcium ions in the effect of epinephrine on cardiac cyclic adenosine 3′, 5′-monophosphate, phosphorylase kinase, and phosphorylase . Molec Pharmacol 4:522-530, 1968;.
35 +
Sattin A, Rall TW:  Effect of adenosine and adenine nucleotides on the cyclic adenosine 3′, 5′-phosphate content of guinea pig cerebral cortex slices . Molec Pharmacol 6:13-23, 1970;.
36 +
Bonner JT:  Hormones in social amoebae and mammals . Sci Amer 220: 78-91, 1969;.
37 +
Salomon Y, Schramm M:  A specific binding site for 3′, 5′-cyclic AMP in rat parotid microsomes . Biochem Biophys Res Commun 38:106-111, 1970;.
38 +
Cheung WY:  Adenosine 3′, 5′-monophosphate: Demonstration of a binding site specific for the cyclic nucleotide . Life Sci 9:861-868, 1970;.
39 +
Hardman JG, Sutherland EW:  Guanyl cyclase, an enzyme catalyzing formation of guanosine 3′, 5′-monophosphate from guanosine triphosphate . J Biol Chem 244:6363-6370, 1969;.
40 +
Ishikawa E, Ishikawa S, Davis JW, et al:  Determination of guanosine 3′, 5′-monophosphate in tissues and of guanyl cylase in rat intestine . J Biol Chem 244: 6371-6362, 1969;.
41 +
Hardman JG, Davis JW, Sutherland EW:  Effects of some hormonal and other factors on excretion of guanosine 3′, 5′-monophosphate and adenosine 3′, 5′-mono-ophosphate in rat urine . J Biol Chem 244: 6354-6362, 1969;.
42 +
Chase LR, Aurbach GD:  Parathyroid function and renal excretion of 3′, 5′-adenylic acid . Proc Nat Acad Sci 58:518-525, 1967;.
43 +
Kaminsky NI, Broadus AE, Hardman JG, et al:  Effects of glucagon and parathyroid hormone on plasma and urinary cyclic AMP in man . J Clin Invest 48:42a, 1969;.
44 +
Broadus AE, Kaminsky NI, Hardman JG, et al:  Kinetic parameters and renal clearances of plasma cyclic AMP and cyclic GMP in man . Clin Res 18:73, 1970;.
45 +
Kaminsky NI, Ball JH, Broadus AE, et al:  Hormonal effects on extracellular cyclic nucleotides in man . Clin Res 18:528, 1970;.
46 +
Chase LR, Melson GL, Aurbach GD:  Pseudohypoparathyroidism: Defective excretion of 3′, 5′-AMP in response to parathyroid hormone . J Clin Invest 48:1832-1844;,1969.
47 +
Orloff J, Handler J:  Role of adenosine 3′, 5′-phosphate in the action of antidiuretic hormone . Amer J Med 42:757-768, 1967;.
48 +
Melson GL, Chase LR, Aurbach GD:  Parathyroid hormone-sensitive adenyl cyclase in isolated renal tubules . Endocrinology 86:511-518, 1970;.
49 +
Broadus AE, Northcutt RC, Hardman JG, et al:  Effects of glucagon on cyclic AMP and cyclic GMP levels in human plasma and urine . Clin Res 17:65, 1970;.
50 +
Ball JH, Kaminsky NI, Broadus AE, et al:  Effects of catecholamines and adrenergic blocking agents on cyclic nucleotides in human plasma . Clin Res 18:336, 1970;.
51 +
George WJ, Poison JB, O'Toole AG, et al:  Elevation of guanosine 3′, 5′-cyclic phosphate in rat heart after perfusion with acetylcholine . Proc Nat Acad Sci 66:398-403, 1970;.
52 +
Taylor AL, Davis BB, Pawlson LG, et al:  Factors influencing urinary excretion of 3′, 5′-adenosine monophosphate in humans . J Clin Endocr 30:316-324, 1970;.
53 +
Paul MI, Ditzion BR, Janowsky DS:  Affective illness and cyclic AMP excretion . Lancet 1:88, 1970;.
54 +
Abdulla YH, Hamadah K:  Cyclic adenosine 3′, 5′-monophosphate in depression and mania . Lancet 1:378-381, 1970;.
55 +
Paul MI, Ditzion BR, Pauk GL, et al:  Urinary adenosine 3′, 5′-monophosphate excretion in affective disorders . Amer J Psychiat 126:1493-1498, 1968;.
56 +
Szentivanyi A:  The beta adrenergic theory of the atopic abnormality in bronchial asthma . J Allerg 442:203-232, 1968;.
57 +
Beavo JA, Hardman JG, Sutherland EW:  Hydrolysis of guanosine and adenosine 3′, 5′-monophosphates by rat and bovine tissues . J Biol Chem , to be published.
58 +
Cheung WY:  Cyclic 3′, 5′-nucleotide phosphodiesterase: Demonstration of an activator . Biochem Biophys Res Commun 38:533-538, 1970;.
59 +
Murad F, Rall TW, Vaughan M:  Conditions for the formation, partial purification, and assay of an inhibitor of adenosine 3′, 5′-monophosphate . Biochim Biophys Acta 192:430-445, 1969;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Makman RS, Sutherland EW:  Adenosine 3′, 5′-phosphate in Escherichia coli . J Biol Chem 240:1309-1314, 1965;.
2 +
Pastan I, Perlman R:  Cyclic adenosine monophosphate in bacteria . Science 169:339-344, 1970;.
3 +
Sutherland EW, Butcher RW, Robison GA, et al:  The role of adenosine 3′, 5′-monophosphate in hormone action , in Karlson P (ed): Wirkungsmechanismen der Hormone . Berlin, Springer-Verlag, 1967;, pp 1-32.
4 +
Sutherland EW, Robison GA, Butcher RW:  Some aspects of the biological role of adenosine 3′, 5′-monophosphate (cyclic AMP) . Circulation 37:279-306, 1968;.
5 +
Sutherland EW, Robison GA:  The role of cyclic AMP in the control of carbohydrate metabolism . Diabetes 18:797-819, 1969;.
6 +
Robison GA, Butcher RW, Sutherland EW:  On the relation of hormone receptors to adenyl cyclase , in Danielli JF, Moran JF, Triggle DJ, Fundamental Concepts in Drug-Receptor Interactions . London, Academic Press, 1969;, pp 59-91.
7 +
Davoren PR, Sutherland EW:  The cellular location of adenyl cyclase in the pigeon erythrocyte . J Biol Chem 238:3016-3023, 1963;.
8 +
Øye I, Sutherland EW:  Effect of epinephrine and other agents on adenyl cyclase in cell membrane of avian erythrocytes . Biochim Biophy Acta 127:347-354, 1966;.
9 +
Rosen OM, Rosen SM:  Properties of an adenyl cyclase partially purified from frog erythrocytes . Arch Biochem 131:449-456, 1969;.
10 +
Pohl SL, Birnbaumer L, Rodbell M:  Glucagon-sensitive adenyl cyclase in plasma membrane of hepatic parenchymal cell . Science 164:566-567, 1969;.
11 +
Lefkowitz RJ, Roth J, Pricer W, et al:  ACTH receptors in the adrenal: Specific binding of ACTH-125 I and its relation to adenyl cyclase . Proc Nat Acad Sci USA 65:745-752, 1970;.
12 +
Rabinowitz M, Desalles L, Meisler J, et al:  Distribution of adenyl-cyclase activity in rabbit skeletal muscle fractions . Biochim Biophys Acta 97:29-36, 1965;.
13 +
Entman ML, Levey GS, Epstein SE:  Demonstration of adenyl cyclase activity in canine cardiac sarcoplasmic reticulum . Biochem Biophys Res Commun 35:729-733, 1969;.
14 +
Butcher RW, Sutherland EW:  Purification and properties of cyclic 3′, 5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′, 5′-phosphate in human urine . J Biol Chem 237:1244-1250, 1962;.
15 +
Cheung WY:  Properties of cyclic 3′, 5′-nucleotide phosphodiesterase from rat brain . Biochemistry 6:1079-1087, 1967;.
16 +
Moore PF:  Effects of diazoxide and benzothiadiazine diuretics upon phosphodiesterase . Ann NY Acad Sci 150:256-260, 1968;.
17 +
Honda F, Imamura J:  Inhibition of cyclic 3′, 5′-nucleotide phosphodiesterase by phenothiazine and reserpine derivatives . Biochim Biophys Acta 161:267-269, 1968;.
18 +
O'Dea RF, Haddox MK, Goldberg ND:  Kinetic analysis of a soluble rat brain cyclic nucleotide phosphodiesterase , abstracted. Fed Proc 29:473, 1970;.
19 +
Robison GA, Sutherland EW:  Sympathin E, sympathin I, and the intracellular level of cyclic AMP . Circ Res 27 ( (suppl 1) ): 147-161, 1970;.
20 +
Butcher RW, Baird CE:  Effects of prostaglandins on adenosine 3′, 5′-monophosphate levels in fat and other tissues . J Biol Chem 243:1713-1717, 1968;.
21 +
Abe K, Robison GA, Liddle GW, et al:  Role of cyclic AMP in mediating effects of MSH, norepinephrine, and melatonin on frog skin color . Endocrinology 85:674-682, 1969;.
22 +
Jefferson LS, Exton JH, Butcher RW, et al:  Role of adenosine 3′, 5′-monophosphate in the effects of insulin and antiinsulin serum on liver metabolism . J Biol Chem 243:1031-1038, 1968;.
23 +
Butcher RW, Baird CE, Sutherland EW:  Effects of lipolytic and antilipolytic substances on adenosine 3′, 5′-monophosphate levels in isolated fat cells . J Biol Chem 243:1705-1712, 1968;.
24 +
Chesney TM, Schofield JG:  Studies on the secretion of pancreatic glucagon . Diabetes 18:627-632, 1969;.
25 +
Friedmann N, Exton JH, Park CR:  Interaction of adrenal steroids and glucagon on gluconeogenesis in perfused rat liver . Biochem Biophys Res Commun 29: 113-119, 1967;.
26 +
Moskowitz J, Fain JN:  Stimulation by growth hormone and dexamethasone of labeled cyclic adenosine 3′, 5′-monophosphate accumulation by white fat cells . J Biol Chem 245:1101-1107, 1970;.
27 +
Breckenridge BM:  Cyclic AMP and drug action . Ann Rev Pharmacol 10:19-34, 1970;.
28 +
Walsh DA, Perkins JP, Krebs EG:  An adenosine 3′, 5′-monophosphate-dependent protein kinase from rabbit skeletal muscle . J Biol Chem 243:3763-3765, 1968;.
29 +
Kuo JF, Greengard P:  Widespread occurrence of adenosine 3′, 5′-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom . Proc Nat Acad Sci 64:1349-1355, 1969;.
30 +
Gill GN, Garren LD:  A cyclic 3′, 5′-adenosine monophosphate dependent protein kinase from adrenal cortex: Comparison with a cyclic AMP binding protein . Biochem Biophys Res Commun 39:335-343, 1970;.
31 +
Somlyo AV, Haeusler G, Somlyo AP:  Cyclic adenosine monophosphate: Potassium-dependent action on vascular smooth muscle membrane potential . Science 169:490-491, 1970;.
32 +
Robison GA, Butcher RW, Sutherland EW: Cyclic AMP . New York, Academic Press Inc, to be published.
33 +
Lundholm L, Rall TW, Vamos N:  Influence of K-ions and adrenaline on the adnosine 3′, 5′-monophosphate content in rat diaphragm . Acta Physiol Scand 70:127-128, 1967;.
34 +
Namm DH, Mayer SE, Maltbie M:  Role of potassium and calcium ions in the effect of epinephrine on cardiac cyclic adenosine 3′, 5′-monophosphate, phosphorylase kinase, and phosphorylase . Molec Pharmacol 4:522-530, 1968;.
35 +
Sattin A, Rall TW:  Effect of adenosine and adenine nucleotides on the cyclic adenosine 3′, 5′-phosphate content of guinea pig cerebral cortex slices . Molec Pharmacol 6:13-23, 1970;.
36 +
Bonner JT:  Hormones in social amoebae and mammals . Sci Amer 220: 78-91, 1969;.
37 +
Salomon Y, Schramm M:  A specific binding site for 3′, 5′-cyclic AMP in rat parotid microsomes . Biochem Biophys Res Commun 38:106-111, 1970;.
38 +
Cheung WY:  Adenosine 3′, 5′-monophosphate: Demonstration of a binding site specific for the cyclic nucleotide . Life Sci 9:861-868, 1970;.
39 +
Hardman JG, Sutherland EW:  Guanyl cyclase, an enzyme catalyzing formation of guanosine 3′, 5′-monophosphate from guanosine triphosphate . J Biol Chem 244:6363-6370, 1969;.
40 +
Ishikawa E, Ishikawa S, Davis JW, et al:  Determination of guanosine 3′, 5′-monophosphate in tissues and of guanyl cylase in rat intestine . J Biol Chem 244: 6371-6362, 1969;.
41 +
Hardman JG, Davis JW, Sutherland EW:  Effects of some hormonal and other factors on excretion of guanosine 3′, 5′-monophosphate and adenosine 3′, 5′-mono-ophosphate in rat urine . J Biol Chem 244: 6354-6362, 1969;.
42 +
Chase LR, Aurbach GD:  Parathyroid function and renal excretion of 3′, 5′-adenylic acid . Proc Nat Acad Sci 58:518-525, 1967;.
43 +
Kaminsky NI, Broadus AE, Hardman JG, et al:  Effects of glucagon and parathyroid hormone on plasma and urinary cyclic AMP in man . J Clin Invest 48:42a, 1969;.
44 +
Broadus AE, Kaminsky NI, Hardman JG, et al:  Kinetic parameters and renal clearances of plasma cyclic AMP and cyclic GMP in man . Clin Res 18:73, 1970;.
45 +
Kaminsky NI, Ball JH, Broadus AE, et al:  Hormonal effects on extracellular cyclic nucleotides in man . Clin Res 18:528, 1970;.
46 +
Chase LR, Melson GL, Aurbach GD:  Pseudohypoparathyroidism: Defective excretion of 3′, 5′-AMP in response to parathyroid hormone . J Clin Invest 48:1832-1844;,1969.
47 +
Orloff J, Handler J:  Role of adenosine 3′, 5′-phosphate in the action of antidiuretic hormone . Amer J Med 42:757-768, 1967;.
48 +
Melson GL, Chase LR, Aurbach GD:  Parathyroid hormone-sensitive adenyl cyclase in isolated renal tubules . Endocrinology 86:511-518, 1970;.
49 +
Broadus AE, Northcutt RC, Hardman JG, et al:  Effects of glucagon on cyclic AMP and cyclic GMP levels in human plasma and urine . Clin Res 17:65, 1970;.
50 +
Ball JH, Kaminsky NI, Broadus AE, et al:  Effects of catecholamines and adrenergic blocking agents on cyclic nucleotides in human plasma . Clin Res 18:336, 1970;.
51 +
George WJ, Poison JB, O'Toole AG, et al:  Elevation of guanosine 3′, 5′-cyclic phosphate in rat heart after perfusion with acetylcholine . Proc Nat Acad Sci 66:398-403, 1970;.
52 +
Taylor AL, Davis BB, Pawlson LG, et al:  Factors influencing urinary excretion of 3′, 5′-adenosine monophosphate in humans . J Clin Endocr 30:316-324, 1970;.
53 +
Paul MI, Ditzion BR, Janowsky DS:  Affective illness and cyclic AMP excretion . Lancet 1:88, 1970;.
54 +
Abdulla YH, Hamadah K:  Cyclic adenosine 3′, 5′-monophosphate in depression and mania . Lancet 1:378-381, 1970;.
55 +
Paul MI, Ditzion BR, Pauk GL, et al:  Urinary adenosine 3′, 5′-monophosphate excretion in affective disorders . Amer J Psychiat 126:1493-1498, 1968;.
56 +
Szentivanyi A:  The beta adrenergic theory of the atopic abnormality in bronchial asthma . J Allerg 442:203-232, 1968;.
57 +
Beavo JA, Hardman JG, Sutherland EW:  Hydrolysis of guanosine and adenosine 3′, 5′-monophosphates by rat and bovine tissues . J Biol Chem , to be published.
58 +
Cheung WY:  Cyclic 3′, 5′-nucleotide phosphodiesterase: Demonstration of an activator . Biochem Biophys Res Commun 38:533-538, 1970;.
59 +
Murad F, Rall TW, Vaughan M:  Conditions for the formation, partial purification, and assay of an inhibitor of adenosine 3′, 5′-monophosphate . Biochim Biophys Acta 192:430-445, 1969;.

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