Paton, David M.

English

AJOL - African Journals Online

656LKW 50S.A. TYDSKRIF VIR GENEESKUNDE(Byvoegsel- 5uid-Afrikaanse Tydskrif vir Laborarorillm- en Kliniekwerk)7 Augustus 1965THE CATECHOL AMINES AND THEIR RECEPTORSDAVID M. PATON,* M.B., CH.B. (CAPE TOWN), Formerly of The DeparTmenT of Physiology and Pharmacology,UniversiTy of Cape T.ownIn 1905, Dale showed in a series of classical experimentsthat pretreatment with ergot not only abolished the pressoraction of adrenaline but also reversed it, producing adepressor effect.'" Thus he was the first to show that thecatechol amines (adrenaline and noradrenaline) act on atleast 2 types of receptors. The findings that adrenaline andnoradrenaline, though chemically very similar, producequalitatively different effects on some tissues can only beinterpreted in this way as well.'" The receptors on whichadrenergic drugs act, were named the alpha and betareceptors by AhJquist in 1948.3 Recent research has pro-vided drugs which will selectively prevent the action ofthe catechol amines on either the alpha or the betareceptors.'In this article the effect of adrenergic drugs on thecardiovascular system and the modifying effect of blockingagents will be discussed, while mention will be made ofreceptors present in other body tissues. Finally, recentresearch into the basic mechanism of action of adrenergicdrugs will be referred to.THE EfFECT OF CATECHOL AMI rES ON THECARDIOVASCULAR SYSTEMA. In The Normal AnimalNoradrenaline is a net vasoconstrictor; consequently,the total peripheral resistance (TPR) is increased. Noradre-naline also increases the contractile force of the heart. Thesystolic blood pressure is raised owing to the increase inTPR and in cardiac contractility. The rise in diastolicpressure results from the increased TPR. In the intactanimal, the raised mean blood pressure causes a reflexlyinduced increase in vagal tone with resultant bradycardia.'"Adrenaline produces vasodilatation in skeletal muscleblood-vessels and thus the TPR falls. The cardiac outputand pulse rate increase. The rise in systolic pressure pro-duced results from the increase in cardiac output. Becauseof the reduced TPR, there is a slight fall in the diastolicblood pressure.":Blood-vessels have 2 receptors for adrenergic drugs,":'"Firstly these are the alpha constrictor receptors whichrespond to noradrenaline. Secondly there are beta dilatorreceptors which respond to isoprenaline. Adrenaline stimu-lates both strongly. Alpha constrictor receptors are widelydistributed, but are lacking in the cardiac and cerebralvascular beds." Beta receptors are most active in skeletalmuscle blood-vessels.'"When adrenergic drugs act on the heart directly, theyare acting on the beta receptors only.'"The observed effects of adrenaline and noradrenaline onthe cardiovascular system (see above) can be explained byilssuming that adrenaline acts on both alpha and betareceptors.'" whereas noradrenaline acts primarily on alphareceptors.'" but has. in addition. potent beta actions on theheart.' Thus adrenaline produces vasodilatation in skeletal*Presem address: Department of Pharmacology, Yale Univer-sitv Sch001 of MediCine. 'ew Haven, Conn.. USA.muscle, while elsewhere in the body, with the exception ofthe coronary vessels, both adrenaline and noradrenalineproduce vasoconstriction." The actions of adrenaline andnoradrenaline on the isolated heart are qualitatively andquantitatively similar.'B. After The AdminisTration of Adrenergic BlockingAgenTsThe adrenergic blocking agents may be divided into 2groups, viz.:I. Those That block The alpha recepTOrs. Examples ofsuch drugs are the ergot alkaloids, phenoxybenzamine,phentolamine, dibenamine and chlorpromazine."-,,,1,. Pre-treatment with these drugs produces progressive blockadeof the vasoconstrictor actions of adrenaline and noradrena-line. This leads to a reversal of the pressor action ofadrenaline (as a result of its unopposed action on the betareceptors) and abolition of that of noradrenaline.'" Thereis no antagonism of the direct effects of either adrenalineor noradrenaline on the heart.'"2. Those That block The beta receptors. Examples ofsuch drugs are pronethanol,'o Inderal" and dichloroisopre-naline." These drugs do not block the vasopressor effectof either adrenaline or noradrenaline but antagonize thecardiac actions of both amines and the vasodilatation ofadrenaline.' Thus the administration of adrenaline nowproduces a rise in both systolic and diastolic blood pressurewith bradycardia."It should be noted that many of these blocking agentshave important actions of their own in addition to block-ade of responses to adrenaline and noradrenaline,'THE CLASSIFICATION OF ADRENERGIC RECEPTORSIN OTHER TISSUESThe general effects of adrenaline and noradrenaline havebeen well reviewed elsewhere.""'" The receptors for thevarious organs, etc., have been c!assified by several authors.3._, •. ',"".," The following classification is based on the abovereferences, namely.(a) Alpha recepTOrs. Vascular smooth muscle, pilomotormuscle, the radial fibres of the iris;(b) BeTa receptors. Vascular smooth muscle (in skeletalmuscle), myometrial muscle, cardiac muscle, bron-chial mmcle; and(c) BOTh alpha and beTa receptors. Intestinal smoothmuscle.There has not been universal agreement on the classifi-cation of certain effects of the catechol amines, particularlytheir metabolic effects." A recent article by VoIle reviewsresearch which does not easily accord with traditionalclassifications."THE PHYSIOLOGICAL BASIS FOR THE EFFECTSOF THE CATECHOL AMINESAdrenaline promotes the formation of a cyclic nucleotide.adenosine-3,5-phosphate. The cyclic nucleotide formedstimulates the formation of active phosphorylase whichA CASE OF APROSOPIA ASSOCIATED WITH ANENCEPHALYMICHAEL LEARY,* M.B., CH.B. (CAPE TOWN), D.A., D.C.H., D.OBST. (R.C.O.G.), lane Furse Memorial Hospital,Middelburg, TransvaalS.A. MEDICAL JOURNAL(Supplemem - Sourh African Journal of Laboratory and Clinical Medicine)IIIIIIIIIIIIIIIIIIIII657LCM 51Autopsy ReportDr. H. Caplin reported: 'An anencephalic monster of mostunusual type. The "head" is partly macerated, extremely smalland so grossly distorted as to make it impossible to determinethe landmarks with any degree of certainty (Fig. I). There isno mouth or nose, the ears being fused together in theanterior midline; the right eye and orbit are just definable butthe vault is open with soft red granular tissue projectingthrough It and the flat membrane bones (?parietal, ?occipital)are incompletely fused posteriorly.'Internal examination. 'Neither tongue nor epiglottis can beidentified. Thyroid and hyoid bones not found. Lower part oftrachea and main bronchi normal. Lungs airless, Oesophagusand stomach normal. Heart normal except for patent foramenovale and ductus arteriosus. Intestines normal.'X-ray examillalion (Fig. 2). Postmortem radiographs of thechild show that the general skeletal structure is essentiallynormaL The skull, however, shows marked abnormality. Themedial growth of the mandible appears to have been arrestedat an early stage and maxillary and nasal bones are absent sothat the sphenoid and petrous temporal bones are well s~en.There is evidence of ossification of the medial wall of the rightmonster which forms the basis of this report. Immediatelyafter delivery the apex beat was palpable and the infant wasobserved to make inspiratory movements of the chest After2 minutes the heart stopped. Birth-weight was 1 kg. and thelength 40 cm.REFERENCESI. Dale, H. H. (1905): J. Physiol. (Lond.), 32, 58.2. Idem (1906): Ibid., 34, 163.3. Ahlquist, R. P. (1948): Amer. J. Physiol., 153, 286.4. Burn. J. H. (1963): The Autonomic Nervous S}·stem. Oxford: Black-well.5. Moran, '. C. (1963): Circulation, 28, 987.6. Robson, J. M. and Keele, C. A. (1956): Recent Advallces ill Pharma-cology, 2nd ed. London: Churchill.7. Ginshurg, J. and Cobbold, A. F., in Vane, J. R. et al., eds. (1960):Adrenergic Mechanisms, p. 173. London: Churchill.8. Robson. J. M. and Stacey, R. S. (1962): Recent Advances ill Phar-macology, 3rd cd. London: Chutchill.9. Nickerson. M. (1959): Pharmacol. Rev., 11, 443.10. Black, J. W. and Stephenson. J. S. (1962): Lancet, 2, 311.11. Black, J. W. et al. (1964): Ibid., 1, 1080.12. Slater, I. H. and Powell, C. E. (1959): Pharmacol. Rev.. 11, 462.13. Dornhorst, A. C. and Rohinson, B. F. (1962): Lancet, 2, 314.14. Furchott, R. F. (1959): Pharmacol. Rev., 11, 429.15. Ahlquist, R. P. (1959): Ibid., 11, 441.16. Guyton, A. C. (1961): Textbook of Medical Physiology, 3rd ed.London: Saunders.17. Volle, R. L. (1963): Ann. Rev. Pharmacol., 3, 129.18. Sutherland, E. W. and Rail, T. W. in Vane, J. R. et al., eds. (1960):Op cit.,' p. 295.19. Editorial (1963): S. Afr. Med. J., 37, 316.20. Lundholm. L. and Mohme-Lundbolm, E. in Vane, J. R. et al., eds.(1960): Op. cit.,' p. 305.21. Gaddum, J. H. in Vane, J. R. et al., eds. (1960): Ibid., p. 588.22. Bul bring , E. in Vane, J. R. et al., cds. (1960): Ibid., p. 275.23. Axelsson, J. et al. (1961): J. Physiol., IS6, 357.24. Bueding. E. et al. (1963): Ibid., 166, 8P.25. Schild, H. O. in Vane, J. R. et al., eds. (1960): Op. cit ..7 p. 288.26. Belleau. B. in Vane, J. R. et al., eds. (1960): Ibid., p. 223.27. Futchott. R. F. in Vane, J. R. et al., cds. (1960): Ibid., p. 246.28. Ariens, E. J. in Vane, J. R. et al., cds. (1960): Ibid., p. 253.29. Green, H. D. and Kepchar, J. H. (1959): Physiol. Rev., 39, 617.tween catechol amines, blocking agents and adrenergicreceptors."":SSUMMARYThe effects of adrenaline and noradrenaline on tissues andtheir possible relationship to receptors, are discussed. Themodifying effect of adrenergic blocking agents are outlined.Theories concerning the basic action of the catechol aminesare presented.7 August 1965·Formerly House-surgeon at the Thorpe Cooinbe Maternity Hospital,Walthamstow. London. E17.Anencephaly is the commonest foetal abnormality incom-patible with survival, and the incidence has been given as0·23% of all births.' Cyclopia in association with anence-phaly is fairly common but association with aprosopia-failure of development of facial structures-appears to berare enough to warrant the recording of the following case.Case ReportI.M., a 19-year-old White housewife, a primagravida, wasfirst seen when 28-weeks pregnant. She had first felt foetalmovements 4 weeks before. Her height was 168·75 cm; sheweighed 66 kg. and her Hb. was 8·2 G/l00 m\. Her bloodpressure was 100/70 mm.Hg. The urine, serological tests andchest X-ray examination were normal and she appeared to bein good health.She was next seen 4 weeks later when the urine and bloodpressure were again normal, but her weight had increased by3·5 kg. and the height of the uterine fundus was greater thanthat expected for the estimated period of gestation. There wasevidence of slight hydramnios.Twelve days later the patient was admitted to hospital inlabour. The uterus was enlarged to the level of the xiphister-num and there was marked hydramnios. A normal first stagewas followed by the rapid delivery of the anencephalicthen in turn stimulates glycogenlysis. Thus, when activatedin liver, an end-product is glucose, while lactate is formedby skeletal muscle. There is some correlation between thephosphorylase concentration in the heart and the effects ofthe catechol amines on cardiac contractility. This wouldsuggest that the beta receptors for cardiac contractility arevery similar to, or identical with, those for the formationof the cyclic nucleotide. 1S A 'cyclase system' may be theactual beta receptor, involving cyclase, magnesium ionsand ATP.'· There is no evidence that the vascular alphareceptors have anything to do with the formation of thecyclic nucleotide.1S It has also been claimed that theinhibition of plain muscle is due to the accumulation oflactic acid,'" but not all authors agree with this theory."Recent advances in the methods used for measuring theelectrophysical changes of muscle have also provided moreevidence about the action of the catechol amines. Studieshave suggested that adrenaline causes relaxation, secon-dary to metabolic changes. Relaxation may be due to anincrease in the amount of energy available for the sodiumpump. Adrenaline has also a direct effect causing depola-rization and thus contraction. The action in any situationis thus the net result of these two actions. When the trans-membrane potential is high, the direct depolarizing actionwill predominate causing contraction. When the trans-membrane potential is low, adrenaline will cause a rise inpotential and thus relaxation.""'" However, the aboveexplanation has been contested."There has also been much research performed on thebiochemical, structural and functional relationships be-

The catechol amines and their receptors

https://www.ajol.info/index.php/samj/article/download/185156/174484

The catechol amines and their receptors

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online