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Presynaptic action of epineprhine on sympathetic ganglia
Life Sciences Vol . 8 Part I, pp . 1235-1238,1969 . Printed in Great Britain
PR~YäAPTIC ACTICN OF
Pergamon Press
~ SYI~ATI~TIC GuGLIA'
D .D . Christ and 8 . Niahi Neuropi~aiolo® Laboratory Departaent ot Pharaacolegy and Thsrapentica Stritch School of I4sdiciae, Loyola IIniversity ft~xeod, Illinois 60153
(Received 6 June 1969 ; in final form 25 August 1969) Since the initial observation by tlarraasi (1), it has been reported quite frequently that epinephrine is capable of dspreasing gaaglionic tranaaiseion (2-5) .
Yet the aechaaiaa of
this depression has sot been clearly elucidated .
It has been
suggested that epinephrine i~yperpolarises the postsynaptic aeabraae, thereby decreasing its a=citability (6,7) "
Alternative
aechaaisos include a decrease in the release of traaaaitter, a decrease in the threshold aeabrane potential level of the postsyaaptic aeabraae or a poatsynaptic curare-lüe action. To investigate this problsa intraoellular aicroelectrode recording techniques xere used .
The superior cervical ganglia
xere isolated troa albino rabbits under sodiua pentobarbital anesthesia .
Aa isolated ganglion xas pertused xith xaraed
(36-38°C), aerated Breba solution (8) .
Orthodroaic responses
xere elicited by stiaulation o! the preganglioaic nerve xith a 0 .1 aaec pulse .
Fecordings xere node with 3 ?S äCl aicro-
electrodes (resistance greater than 30 aegohas) inserted is the postganglionic cell body .
'This xorà xas supported by the Institute of Neurological Diseases and Blindness, NIH Grant HB06672-04 and National Science Foundation Great GB-526911 . 1235
PRESYNAPTIC ACTION OF EPI
1256
Vol. 8, No . 21
Addition of epinephrine bitartrate (10 -5M) to the perfusing solution resulted in a rapid blockade of the orthôdroaic cell body action potential, but there xers only wall changes is the resting asabraae potential of the cell body . In a typical ezperiaeat, illustrated by Fig. lA, the orthodroaic response xas reduoed to an $PSP (ezcitatory postsyaaptic potential) .
~inephrine was also very effective is decreasing
the aaplitude of EPSP's xhich xers initially subthreshold . Blockade of the orthodroaic action potential and depresaioa of the SPBP by epinephrine xers both inhibited by phenozybeazaaiae hydrochloride (10 -SK), but not by propraaolol (3 z 10 5H)
.
Thsae concentrations of pheno~beazaaine and propraaolol did not affect the cell body action potential or EPSP . Application of 10-3?1 acetylcholiae chloride produced a constant reproducible depolarising potential .
Spiaephrine
(10-5?i) had no effect on the acetylcholine potentials, even though the orthodromic response xas considerably depressed (Fig . 1B) . On the basis of these results it eeeas likely that epinephrine produces its effect oa the isolated ganglion by decreasing the release of traasaitter iron the presynaptic ter ai.aals .
This is siailar to the concluaioas of Patoa and
Thoapson (9), and Biris and Iiaclntosh (10), xho observed a decrease in the output of acetylcholiae iron isolated ganglia. The effectiveness of the alpha blocker, pheaozybenaaaine, indicates that the presynaptic terainals are endoxed xith alpha adrenoceptive sites .
Vol. 8, No . 21
PRESYNAPTIC ACTION OF EPI
1237
Epi 120 seç
r
Con ACh
+
~IOmV
2o sec
Ep i ACh
FIG. 1
d: The effect of epinephrine oa the ganglion cell re Con - recordings in control sponse to as orthodroaic stiaulus . Srebs solution before upper left) sad 4 sin after coapleting epinephrine perfusion lover right) . - Tspi - recordings 50 sec, 60 sec and 120 sec after beginning 10 5H epinephrine bitartrate perfusion. B: The effect of epinephrine oa the ganglion cell reSpi - 3 apoaae to acetTlcholiae perfusion. Con - ooatrol . aia after be 10-5fI epinephrine bitartrate perfusion. dcetylcholine (dCh vaa applied during the interval betveea the tvo strove .
1238
PRESYNAPTIC ACTION OF EPI
Vol. 8, No . 21
References 1.
A.B . riARRAZZI, J. Pharaacol . ,6~, p .395 C1939) .
2.
S. BÜLBSI1fG, J . Pbyeiol . (London) 10~, p.55 i19~) "
3.
R.J . r1ATTHEYB, J. Pharaacol. 11 , p .433 (1956) .
4.
R.K . SCCLSS and B . LIBHT, J. Ph7siol . (London) ~, p .484 (1961) . --
5.
$.G . PARDC, J. CATC, E. GIJCH and F. ALOH80 de FLCRIDA, J. Pharaaaol. ~, p .296 C1963) "
6.
A. LII11DBlG, Acta Pbssiol . Saand . 26, p .251 C1952) "
7.
Y.C. DE GROAT and R.L . VCLL$, J. Pharoaaol .,~4, p .l (1966).
. 98 . 10 .
R.IS. SCCLFB, J. Ph~eiol . (London ) 1~0, p .572 11955) " i.D .n.~PA~T~H95 a~ . J.Y . THCI~B~, Proc . Iat . Ph9eiol . COnAr. p" R. BIBSS and F .C . I4ACIATaSH, Caned . J. Biochea. PhYSiol . P " 787 (196D .
PR~YäAPTIC ACTICN OF
Pergamon Press
~ SYI~ATI~TIC GuGLIA'
D .D . Christ and 8 . Niahi Neuropi~aiolo® Laboratory Departaent ot Pharaacolegy and Thsrapentica Stritch School of I4sdiciae, Loyola IIniversity ft~xeod, Illinois 60153
(Received 6 June 1969 ; in final form 25 August 1969) Since the initial observation by tlarraasi (1), it has been reported quite frequently that epinephrine is capable of dspreasing gaaglionic tranaaiseion (2-5) .
Yet the aechaaiaa of
this depression has sot been clearly elucidated .
It has been
suggested that epinephrine i~yperpolarises the postsynaptic aeabraae, thereby decreasing its a=citability (6,7) "
Alternative
aechaaisos include a decrease in the release of traaaaitter, a decrease in the threshold aeabrane potential level of the postsyaaptic aeabraae or a poatsynaptic curare-lüe action. To investigate this problsa intraoellular aicroelectrode recording techniques xere used .
The superior cervical ganglia
xere isolated troa albino rabbits under sodiua pentobarbital anesthesia .
Aa isolated ganglion xas pertused xith xaraed
(36-38°C), aerated Breba solution (8) .
Orthodroaic responses
xere elicited by stiaulation o! the preganglioaic nerve xith a 0 .1 aaec pulse .
Fecordings xere node with 3 ?S äCl aicro-
electrodes (resistance greater than 30 aegohas) inserted is the postganglionic cell body .
'This xorà xas supported by the Institute of Neurological Diseases and Blindness, NIH Grant HB06672-04 and National Science Foundation Great GB-526911 . 1235
PRESYNAPTIC ACTION OF EPI
1256
Vol. 8, No . 21
Addition of epinephrine bitartrate (10 -5M) to the perfusing solution resulted in a rapid blockade of the orthôdroaic cell body action potential, but there xers only wall changes is the resting asabraae potential of the cell body . In a typical ezperiaeat, illustrated by Fig. lA, the orthodroaic response xas reduoed to an $PSP (ezcitatory postsyaaptic potential) .
~inephrine was also very effective is decreasing
the aaplitude of EPSP's xhich xers initially subthreshold . Blockade of the orthodroaic action potential and depresaioa of the SPBP by epinephrine xers both inhibited by phenozybeazaaiae hydrochloride (10 -SK), but not by propraaolol (3 z 10 5H)
.
Thsae concentrations of pheno~beazaaine and propraaolol did not affect the cell body action potential or EPSP . Application of 10-3?1 acetylcholiae chloride produced a constant reproducible depolarising potential .
Spiaephrine
(10-5?i) had no effect on the acetylcholine potentials, even though the orthodromic response xas considerably depressed (Fig . 1B) . On the basis of these results it eeeas likely that epinephrine produces its effect oa the isolated ganglion by decreasing the release of traasaitter iron the presynaptic ter ai.aals .
This is siailar to the concluaioas of Patoa and
Thoapson (9), and Biris and Iiaclntosh (10), xho observed a decrease in the output of acetylcholiae iron isolated ganglia. The effectiveness of the alpha blocker, pheaozybenaaaine, indicates that the presynaptic terainals are endoxed xith alpha adrenoceptive sites .
Vol. 8, No . 21
PRESYNAPTIC ACTION OF EPI
1237
Epi 120 seç
r
Con ACh
+
~IOmV
2o sec
Ep i ACh
FIG. 1
d: The effect of epinephrine oa the ganglion cell re Con - recordings in control sponse to as orthodroaic stiaulus . Srebs solution before upper left) sad 4 sin after coapleting epinephrine perfusion lover right) . - Tspi - recordings 50 sec, 60 sec and 120 sec after beginning 10 5H epinephrine bitartrate perfusion. B: The effect of epinephrine oa the ganglion cell reSpi - 3 apoaae to acetTlcholiae perfusion. Con - ooatrol . aia after be 10-5fI epinephrine bitartrate perfusion. dcetylcholine (dCh vaa applied during the interval betveea the tvo strove .
1238
PRESYNAPTIC ACTION OF EPI
Vol. 8, No . 21
References 1.
A.B . riARRAZZI, J. Pharaacol . ,6~, p .395 C1939) .
2.
S. BÜLBSI1fG, J . Pbyeiol . (London) 10~, p.55 i19~) "
3.
R.J . r1ATTHEYB, J. Pharaacol. 11 , p .433 (1956) .
4.
R.K . SCCLSS and B . LIBHT, J. Ph7siol . (London) ~, p .484 (1961) . --
5.
$.G . PARDC, J. CATC, E. GIJCH and F. ALOH80 de FLCRIDA, J. Pharaaaol. ~, p .296 C1963) "
6.
A. LII11DBlG, Acta Pbssiol . Saand . 26, p .251 C1952) "
7.
Y.C. DE GROAT and R.L . VCLL$, J. Pharoaaol .,~4, p .l (1966).
. 98 . 10 .
R.IS. SCCLFB, J. Ph~eiol . (London ) 1~0, p .572 11955) " i.D .n.~PA~T~H95 a~ . J.Y . THCI~B~, Proc . Iat . Ph9eiol . COnAr. p" R. BIBSS and F .C . I4ACIATaSH, Caned . J. Biochea. PhYSiol . P " 787 (196D .