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Delineation of β1- and β2-adrenoceptor sites
TIPS - Fehntary I9 12
52
Ddineaticmof PI- and ~~adrenoceptorvitas The b&n of Dr Arnold s letter’ seems to be that since only catecholamine stmctures were used to formulate the dual /3-adtmnxeptor hypothesis any results obta&d with non-catecholaminestructlms am invalid. He furtl~ suggests *&atthese
The value of a receptor classification should be in its ability to provide physiolw gistsand clinicii witha biologicalbasis for understanding the action of agonists and antagonists under physiological and pathological conditions. The dual
‘invalid’nsults could he used to proposea new receptorand nomenclature.I do not find suchargumentspersuasive. The fact that the dual @drenoceptor hypothesis was derived by the determina tion of the relativeqonist activities of certain catecholamines~is not disputed. However, it must be noted that the catecholamines’used to establish the /31-
/3_admnoceptor
and&&aoceptor hypothesisand to sub stantiateir do not all occur naturally. .sinc~ the original classification was based on syntheticsmh-tmes it does not seem logical
to exclude additional data obtained with G&r syntheticsrmctlues.The use of bk& ea cannot simply be dismissed as circular iCSsoningbecausethey‘arecharacterizedin test systemsto begin with’I. This criticism
can apply equally to thz agonists used to defm the receptors initially.
hypothesis
can
is robust enough to withstand such pmb lems. Indeedthe most impressivefeatule 3f the dual &adtenoceptor hypothesis is IY substantial body of supporting evidcn:e (see Ref. 5 for citations) providedby c I(wriments with catecholamine and nC:+ catecholamineJ34renoceptoragonistsa id &3drenoceptorantagonists.
do
this”. A nzcqtor classification which is only appiicahleto the fiit compounds used lo deft it is of very little value. AmoW
statementthatthe use of blockersand noncatecholamine agonists is acceptable if a new nomenclatureis pmposed. could lead to a plethora of systems which confuse
ratherthan aid our understandingof body function. Everyeffortshouldbe made to t3 new data into an existinghypothesisbefore invoking a new one. In any body of work resultsoccur which do not immediately fit into the expected pattern.Such resultsmay challenge the hypothesisbut some of those results may themselves be challenged because of inadequacies in control ,of experimental conditions. experimqtal design, analysis or other factors. I beli&e thatthe &- and@uJrenoceptorhypothesis
ResdingM I Amold.A. ( 198I) Trends f/~annoro/.&i. 3. p 7 2 L.&s. A. M.. Anwld. A.. McAuiil I. P.. Luduelm. F. P.andBmwn.Jr.T.G. (1%7)Na1 we (London) 214.597-598 3 Am1d.A. (I972)IIFarmacoEd.Sci. 27.7%’ Jo 4 AriW.E. 1. (1981) Tmds Phomtacol.SCI 2. 171-173 5 Daly. M. 1. andLevyG. P. (1979) in Trend in Autonomic Phammolog.v (Kalsner.S., 01.). Vol. I. PP.347-385. UrbanandSchwaruznb rg, Baltimore. Munich M. 1. DA’>Y
52
Ddineaticmof PI- and ~~adrenoceptorvitas The b&n of Dr Arnold s letter’ seems to be that since only catecholamine stmctures were used to formulate the dual /3-adtmnxeptor hypothesis any results obta&d with non-catecholaminestructlms am invalid. He furtl~ suggests *&atthese
The value of a receptor classification should be in its ability to provide physiolw gistsand clinicii witha biologicalbasis for understanding the action of agonists and antagonists under physiological and pathological conditions. The dual
‘invalid’nsults could he used to proposea new receptorand nomenclature.I do not find suchargumentspersuasive. The fact that the dual @drenoceptor hypothesis was derived by the determina tion of the relativeqonist activities of certain catecholamines~is not disputed. However, it must be noted that the catecholamines’used to establish the /31-
/3_admnoceptor
and&&aoceptor hypothesisand to sub stantiateir do not all occur naturally. .sinc~ the original classification was based on syntheticsmh-tmes it does not seem logical
to exclude additional data obtained with G&r syntheticsrmctlues.The use of bk& ea cannot simply be dismissed as circular iCSsoningbecausethey‘arecharacterizedin test systemsto begin with’I. This criticism
can apply equally to thz agonists used to defm the receptors initially.
hypothesis
can
is robust enough to withstand such pmb lems. Indeedthe most impressivefeatule 3f the dual &adtenoceptor hypothesis is IY substantial body of supporting evidcn:e (see Ref. 5 for citations) providedby c I(wriments with catecholamine and nC:+ catecholamineJ34renoceptoragonistsa id &3drenoceptorantagonists.
do
this”. A nzcqtor classification which is only appiicahleto the fiit compounds used lo deft it is of very little value. AmoW
statementthatthe use of blockersand noncatecholamine agonists is acceptable if a new nomenclatureis pmposed. could lead to a plethora of systems which confuse
ratherthan aid our understandingof body function. Everyeffortshouldbe made to t3 new data into an existinghypothesisbefore invoking a new one. In any body of work resultsoccur which do not immediately fit into the expected pattern.Such resultsmay challenge the hypothesisbut some of those results may themselves be challenged because of inadequacies in control ,of experimental conditions. experimqtal design, analysis or other factors. I beli&e thatthe &- and@uJrenoceptorhypothesis
ResdingM I Amold.A. ( 198I) Trends f/~annoro/.&i. 3. p 7 2 L.&s. A. M.. Anwld. A.. McAuiil I. P.. Luduelm. F. P.andBmwn.Jr.T.G. (1%7)Na1 we (London) 214.597-598 3 Am1d.A. (I972)IIFarmacoEd.Sci. 27.7%’ Jo 4 AriW.E. 1. (1981) Tmds Phomtacol.SCI 2. 171-173 5 Daly. M. 1. andLevyG. P. (1979) in Trend in Autonomic Phammolog.v (Kalsner.S., 01.). Vol. I. PP.347-385. UrbanandSchwaruznb rg, Baltimore. Munich M. 1. DA’>Y