- Email: [email protected]
α1-Adrenergic action: only calcium?
489
TIPS - December 1983 relapse in man and, as Del Soldato suggested, may assist in the search for drugs to treat IBD in man. Overall, the meeting was most useful in bringing together research workers and clinicians working in different disciplines to discuss diseases of the lower bowel, knowledge of which is still in its infancy. It
was certainly a good opportunity to have a spring-cleaning of thoughts. K D. RAINSFORD
Department of Pharmacology, University of Cambridge, Hills Road, Cambridge, UK.
Note The proceedings of the symposium have been published: New Trends in
the Pathophysiology and Therapy of the Large Bowel, edited by L. Barbara, M. Miglioli and S. F. Phillips, Elsevier, Amsterdam, 1983
Q
I
Current
awareness
series K e y d e v e l o p m e n t s in p h a r m a c o l o g y
processes that link the activation of ct,adrenoceptors to the final effects.
,-Adrenergic action: only calcium? The mechanism of signal transduction that follows ctl-adrenergic activation has remained obscure in spite of the efforts of many researchers, et~-Adrenoceptors seem to be linked to a caicium signailing-process which involves phosphatidylinositol turnoveP-3. A large amount of evidence supporting a role of calcium in oa-adrenergic action already exists. It has been observed that o.-adrenergic activation, as well as activation by other hormones and neurotransmitters) such as vasopressin, angiotensin I1 or muscarinic-cholinergic agonists) result in significant changes in the steady state concentration of free calcium in the different cell compartments; the data suggest that calcium may act as a second messenger or coupling factor (reviewed in Ref. 4). However, at least three groups have recently proposed that the process of signal transduction for c~l-adrenergic agents may involve factors besides calcium and that it may involve more than one pathway s-7. The evidence for this can be sammarized as shown below. (1) The metabolic effects of o,-adrenergic agents in liver cells, depend to a much lesser extent on the presence of extracellular calcium than those of vasopressin or angiotensin I1 (Ref. 8). (2) It has been reported that under conditions of calcium depletion, a~-adrenergic agents (but not vasopressin or angiotensin II) elevate cAMP levels7. (3) Insulin diminishes the activation of phosphorylase produced by ota-adrenergic amines but not the activation of this enzyme produced through the action of vasopressin 9. (4) In hepatocytes from hypothyroid animais the glycogenolytic action of vasopressin, angiotensin II or the calcium ionophore A23187 are nearly abolished, whereas
al-adrenergic activation results in clear stimulation of this metabolic pathwayS; these latter data indicate that a~-adrenergic activation can produce metabolic effects in cells which are insensitive to calciumsignalling. (5) The stimulation of secretion produced by al-adrenergic agents is markedly decreased in parotid cells from old rats as compared with that in cells from young animals; there was no significant change in the number of o.-adrenoceptors or in the response produced by cholinergic activation of the cells~. Thus, it is becoming clear that our present schemes for hormone action are incomplete and that the actions of a~-adrenergic amines are affected by the experimental conditions to an extent different from those of other agents (which supposedly act through the same mechanism). Further research is urgently required to clarify the
J. ADOLFO GARCfA-S,g.INZ AND SILVIA CORVERA
Departamento de Bioenerg~tica, Centro de lnvestigac~ones en Flslologfa Celular; Universidad Nacional Aut6noma de M~xtco. Apartado Postal 70-600 04510, Mdxico, DF.
Reading list 1 Michell, R. H. (1975) Biochim. Bzophys. Acta 415, 81-147 2 Jones, L. M. and Mmhell, R. H. 0978)Bzochem. Soc. Trans. 6, 673-688 3 Fain, J.N andGarcia-S/fin~,J A (1980)LlfeSo. 26, 1183-1194 4 Williamson, J R., Cooper, R. H. and Hack, J B. (1981) Bzoctum. Biophys. Acta 639, 243-295 5 Corvera, S and Garcia~S~nz. J A. (1983) FEBS Lett. 153, 366-368 6 Bodner, L.,Hoopes, M T.,Gee, M.,Ito, H.,Roth, G. S. and Baum, B. J (1983)J. Biol. Chem. 258, 2774-2777 7 Morgan, N G., Blackng)te, P. F. and Exton, J H. (1983)J. Biol. Chem. 258, 5103-5109 8 Corvera, S and Garcia-S/dnz, J. A. (1982) Life SCL 31,2493-2498 9 Dehaye, J. P, Hugh¢*, B P, Blackmore, P. F and Exton, J. H ( 1981 ) Biochem. J. 194,949-956
Can Hertz be harmful? An endocrine action of extremely low frequency electromagnetic fields In less than a century, a network of high voltage electrical distribution lines has been laid across the globe. Simultaneously, the world has been bathed in a sea of electromagnetic communications. Eskimos trudging the boreal snows, Bedouin gazing at the stars over Sinai and Americans relaxing in their homes of an evening need only to turn on a radio to be made aware of the electromagnetic ambience in which they live. Mankind is now continuously and intimately exposed to culturally produced electromagnetic fields.
The heaviest exposure to culturally produced fields derives from FM radio broadcasts which fail within the 30-300 mHz, or very high frequency (VHF) range. The distribution and utilization of electricity, however, is the major source of exposure to fields with frequencies in the 0-300 Hz, or extremely low frequency (ELF) range. At a frequency of 10 Hz, the solar flux on the earth does not exceed 1 mV m -1. In American homes, however, 60 Hz fields of 1-10 V m -1 are typically present. Fields may be as high as 250 V m -1 near electric blankets.
19~3.E,lsevlcrStactg~~ t 5
B V . AJrsterdam 0165- 6147tR32501Ill
TIPS - December 1983 relapse in man and, as Del Soldato suggested, may assist in the search for drugs to treat IBD in man. Overall, the meeting was most useful in bringing together research workers and clinicians working in different disciplines to discuss diseases of the lower bowel, knowledge of which is still in its infancy. It
was certainly a good opportunity to have a spring-cleaning of thoughts. K D. RAINSFORD
Department of Pharmacology, University of Cambridge, Hills Road, Cambridge, UK.
Note The proceedings of the symposium have been published: New Trends in
the Pathophysiology and Therapy of the Large Bowel, edited by L. Barbara, M. Miglioli and S. F. Phillips, Elsevier, Amsterdam, 1983
Q
I
Current
awareness
series K e y d e v e l o p m e n t s in p h a r m a c o l o g y
processes that link the activation of ct,adrenoceptors to the final effects.
,-Adrenergic action: only calcium? The mechanism of signal transduction that follows ctl-adrenergic activation has remained obscure in spite of the efforts of many researchers, et~-Adrenoceptors seem to be linked to a caicium signailing-process which involves phosphatidylinositol turnoveP-3. A large amount of evidence supporting a role of calcium in oa-adrenergic action already exists. It has been observed that o.-adrenergic activation, as well as activation by other hormones and neurotransmitters) such as vasopressin, angiotensin I1 or muscarinic-cholinergic agonists) result in significant changes in the steady state concentration of free calcium in the different cell compartments; the data suggest that calcium may act as a second messenger or coupling factor (reviewed in Ref. 4). However, at least three groups have recently proposed that the process of signal transduction for c~l-adrenergic agents may involve factors besides calcium and that it may involve more than one pathway s-7. The evidence for this can be sammarized as shown below. (1) The metabolic effects of o,-adrenergic agents in liver cells, depend to a much lesser extent on the presence of extracellular calcium than those of vasopressin or angiotensin I1 (Ref. 8). (2) It has been reported that under conditions of calcium depletion, a~-adrenergic agents (but not vasopressin or angiotensin II) elevate cAMP levels7. (3) Insulin diminishes the activation of phosphorylase produced by ota-adrenergic amines but not the activation of this enzyme produced through the action of vasopressin 9. (4) In hepatocytes from hypothyroid animais the glycogenolytic action of vasopressin, angiotensin II or the calcium ionophore A23187 are nearly abolished, whereas
al-adrenergic activation results in clear stimulation of this metabolic pathwayS; these latter data indicate that a~-adrenergic activation can produce metabolic effects in cells which are insensitive to calciumsignalling. (5) The stimulation of secretion produced by al-adrenergic agents is markedly decreased in parotid cells from old rats as compared with that in cells from young animals; there was no significant change in the number of o.-adrenoceptors or in the response produced by cholinergic activation of the cells~. Thus, it is becoming clear that our present schemes for hormone action are incomplete and that the actions of a~-adrenergic amines are affected by the experimental conditions to an extent different from those of other agents (which supposedly act through the same mechanism). Further research is urgently required to clarify the
J. ADOLFO GARCfA-S,g.INZ AND SILVIA CORVERA
Departamento de Bioenerg~tica, Centro de lnvestigac~ones en Flslologfa Celular; Universidad Nacional Aut6noma de M~xtco. Apartado Postal 70-600 04510, Mdxico, DF.
Reading list 1 Michell, R. H. (1975) Biochim. Bzophys. Acta 415, 81-147 2 Jones, L. M. and Mmhell, R. H. 0978)Bzochem. Soc. Trans. 6, 673-688 3 Fain, J.N andGarcia-S/fin~,J A (1980)LlfeSo. 26, 1183-1194 4 Williamson, J R., Cooper, R. H. and Hack, J B. (1981) Bzoctum. Biophys. Acta 639, 243-295 5 Corvera, S and Garcia~S~nz. J A. (1983) FEBS Lett. 153, 366-368 6 Bodner, L.,Hoopes, M T.,Gee, M.,Ito, H.,Roth, G. S. and Baum, B. J (1983)J. Biol. Chem. 258, 2774-2777 7 Morgan, N G., Blackng)te, P. F. and Exton, J H. (1983)J. Biol. Chem. 258, 5103-5109 8 Corvera, S and Garcia-S/dnz, J. A. (1982) Life SCL 31,2493-2498 9 Dehaye, J. P, Hugh¢*, B P, Blackmore, P. F and Exton, J. H ( 1981 ) Biochem. J. 194,949-956
Can Hertz be harmful? An endocrine action of extremely low frequency electromagnetic fields In less than a century, a network of high voltage electrical distribution lines has been laid across the globe. Simultaneously, the world has been bathed in a sea of electromagnetic communications. Eskimos trudging the boreal snows, Bedouin gazing at the stars over Sinai and Americans relaxing in their homes of an evening need only to turn on a radio to be made aware of the electromagnetic ambience in which they live. Mankind is now continuously and intimately exposed to culturally produced electromagnetic fields.
The heaviest exposure to culturally produced fields derives from FM radio broadcasts which fail within the 30-300 mHz, or very high frequency (VHF) range. The distribution and utilization of electricity, however, is the major source of exposure to fields with frequencies in the 0-300 Hz, or extremely low frequency (ELF) range. At a frequency of 10 Hz, the solar flux on the earth does not exceed 1 mV m -1. In American homes, however, 60 Hz fields of 1-10 V m -1 are typically present. Fields may be as high as 250 V m -1 near electric blankets.
19~3.E,lsevlcrStactg~~ t 5
B V . AJrsterdam 0165- 6147tR32501Ill