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Histamine mediates postsynaptic excitation and presynaptic inhibition in submucous neurons of the guinea pig
$178
MODULATION
OF
GLUTAMATE-MEDIATED
TRANSMISSION
BY
MONOAMINES
AND
PEPTIDES
AT
THE INSECT NEUROMUSCULAR JUNCTION DAISUKE YAMAMOTO and
SACHIYO ISHIKAWA% Lab. Neurophysiol., Mitsubishi-Kasei Inst. Life Sci.,
Machida, Tokyo 194, Japan R e c e n t l y , 12 n e u r o p e p t i d e s w e r e i s o l a t e d f r o m h e a d e x t r a c t s o f t h e c o c k r o a c h a n d t h e i r s t r u c t u r e s were d e t e r m i n e d . A m o n g these, leucomyosuppressin (LMS: pGlu-Asp-Val-Asp-His-Val-PheL e u - A r g - P h e - N H 2) is u n i q u e in t h a t it d e p r e s s e s s p o n t a n e o u s m u s c l e c o n t r a c t i o n s , w h i l e all o t h e r neuropeptides are powerful stimulants. We h a v e d e m o n s t r a t e d t h a t LMS a t t e n u a t e s t h e e v o k e d t r a n s m i t t e r r e l e a s e from t h e p r e s y n a p t i c m e m b r a n e of e x c i t a t o r y m o t o n e u r o n e s t e r m i n a t i n g on t h e skeletal muscle of t h e larval m e a l w o r m Tenebrio molitor. Exogenous arachidonic acid m i m i c s t h e LMS e f f e c t and a lipoxygenase inhibitor nordihydroguairetic acid blocks t h e a c t i o n s of arachidonic a c i d a n d LMS. T h e s e f a c t s a p p e a r to i n d i c a t e t h a t l i p o x y g e n a s e m e t a b o l i t e s of a r a c h i d o n i c a c i d m e d i a t e t h e LMS-induced inhibition of t h e n e u r o m u s c u l a r t r a n s m i s s i o n in insects. In i n s e c t s , it is w e l l - k n o w n t h a t a m o d u l a t o r y n e u r o n e a c c e l e r a t e s t r a n s m i t t e r r e l e a s e at t h e excitatory motoneurone-skeletal m u s c l e j u n c t i o n by r e l e a s i n g o c t o p a m i n e w h i c h s t i m u l a t e s c A M P production in t h e m o t o r n e r v e t e r m i n a l . In c o n t r a s t , no m o d u l a t o r substance that has an i n h i b i t o r y e f f e c t on n e u r o n a l a c t i v i t i e s h a s b e e n e s t a b l i s h e d in i n s e c t s . LMS is t h e m o s t l i k e l y candidate for this role, as elucidated in t h i s p r e s e n t a t i o n . A t l e a s t in t h e m e a l w o r m n e u r o m u s c u l a r junction, dual modulation by t h e o c t o p a m i n e - a d e n y l a t e c y c l a s e s y s t e m and the LMSeicosanoids system of the excitatory transmission takes place. This situation closely parallels what happens at t h e p r e s y n a p t i c terminal of t h e sensory neurones of Aplysia. It is i n t e r e s t i n g to s e e how general t h e dualism of regulation of e x c i t a t o r y synaptic t r a n s m i s s i o n by m o n o a m i n e s and peptides is in o t h e r s y n a p s e s and organisms.
HISTAMINE MEDIATES POSTSYNAPTIC EXCITATION AND PRESYNAPTIC INHIBITION IN SUBMUCOUS NEURONS OF THE GUINEA PIG. TAKAYUKI TOKIMASA and TAKASHI Medicine, Kurume 830, Japan.
AKASU,
Department
of
Physiology,
Kurume
University
School
of
Intracellular recordings were made from submucous plexus neurons of the guinea pig cecum maintained in vitro. Histamine (0.3-10 ~M) produced a dose-dependent membrane depolarization (=12 mV with 3 ~M) in about 26 % of the cells tested. Most of these showed a prominent calcium-activated potassium conductance (AH cells). Histamine-induced depolarization was less often observed in S cells (2 out of 33 cells) and the peak amplitude of the depolarization was less than 5 mV with i0 ~M. The depolarization was due primarily to an inactivation of potassium conductance which is available at the resting membrane potential of -60 mV. Peak amplitude of the fast excitatory postsynaptic potential (EPSP) was depressed by histamine (0.1-10 ~M) in a concentration-dependent manner (=65 % depression with 1 ~M). This was observed even in those cells where histamine did not produce any membrane depolarizations (mostly S cells). The depression of the fast EPSP resulted from presynaptic inhibition of acetylcholine (ACh) release, since membrane depolarizations produced by exogenously applied ACh were not significantly affected by histamine. Histamine-induced depression of ACh release was not affected by pretreatment of the preparation with hyoscine (100 nM) or idazoxan (i00 nM). This implied that histamine-induced depression of ACh release was not due to an activation of presynaptic muscarinic (M2) and adrenergic (~2) receptors. Histamine also reduced the amplitude of the non-cholinergfc, presumably pepti~ergic, slow EPSP by suppressing peptide release from the presynaptic nerve terminals. The peak amplitude of adrenergic inhibitory synaptic potentials was not depressed by histamine, suggesting that histamine receptors do not occur at presynaptic terminals of sympathetic nerve fibres. Both postsynaptic and presynaptic actions of histamine were blocked by cimetidine (I-30 ~M) or ranitidine (1-30 ~M) but not by pyrilamine (30 ~M), implying that receptors involved would be H 2 type.
MODULATION
OF
GLUTAMATE-MEDIATED
TRANSMISSION
BY
MONOAMINES
AND
PEPTIDES
AT
THE INSECT NEUROMUSCULAR JUNCTION DAISUKE YAMAMOTO and
SACHIYO ISHIKAWA% Lab. Neurophysiol., Mitsubishi-Kasei Inst. Life Sci.,
Machida, Tokyo 194, Japan R e c e n t l y , 12 n e u r o p e p t i d e s w e r e i s o l a t e d f r o m h e a d e x t r a c t s o f t h e c o c k r o a c h a n d t h e i r s t r u c t u r e s were d e t e r m i n e d . A m o n g these, leucomyosuppressin (LMS: pGlu-Asp-Val-Asp-His-Val-PheL e u - A r g - P h e - N H 2) is u n i q u e in t h a t it d e p r e s s e s s p o n t a n e o u s m u s c l e c o n t r a c t i o n s , w h i l e all o t h e r neuropeptides are powerful stimulants. We h a v e d e m o n s t r a t e d t h a t LMS a t t e n u a t e s t h e e v o k e d t r a n s m i t t e r r e l e a s e from t h e p r e s y n a p t i c m e m b r a n e of e x c i t a t o r y m o t o n e u r o n e s t e r m i n a t i n g on t h e skeletal muscle of t h e larval m e a l w o r m Tenebrio molitor. Exogenous arachidonic acid m i m i c s t h e LMS e f f e c t and a lipoxygenase inhibitor nordihydroguairetic acid blocks t h e a c t i o n s of arachidonic a c i d a n d LMS. T h e s e f a c t s a p p e a r to i n d i c a t e t h a t l i p o x y g e n a s e m e t a b o l i t e s of a r a c h i d o n i c a c i d m e d i a t e t h e LMS-induced inhibition of t h e n e u r o m u s c u l a r t r a n s m i s s i o n in insects. In i n s e c t s , it is w e l l - k n o w n t h a t a m o d u l a t o r y n e u r o n e a c c e l e r a t e s t r a n s m i t t e r r e l e a s e at t h e excitatory motoneurone-skeletal m u s c l e j u n c t i o n by r e l e a s i n g o c t o p a m i n e w h i c h s t i m u l a t e s c A M P production in t h e m o t o r n e r v e t e r m i n a l . In c o n t r a s t , no m o d u l a t o r substance that has an i n h i b i t o r y e f f e c t on n e u r o n a l a c t i v i t i e s h a s b e e n e s t a b l i s h e d in i n s e c t s . LMS is t h e m o s t l i k e l y candidate for this role, as elucidated in t h i s p r e s e n t a t i o n . A t l e a s t in t h e m e a l w o r m n e u r o m u s c u l a r junction, dual modulation by t h e o c t o p a m i n e - a d e n y l a t e c y c l a s e s y s t e m and the LMSeicosanoids system of the excitatory transmission takes place. This situation closely parallels what happens at t h e p r e s y n a p t i c terminal of t h e sensory neurones of Aplysia. It is i n t e r e s t i n g to s e e how general t h e dualism of regulation of e x c i t a t o r y synaptic t r a n s m i s s i o n by m o n o a m i n e s and peptides is in o t h e r s y n a p s e s and organisms.
HISTAMINE MEDIATES POSTSYNAPTIC EXCITATION AND PRESYNAPTIC INHIBITION IN SUBMUCOUS NEURONS OF THE GUINEA PIG. TAKAYUKI TOKIMASA and TAKASHI Medicine, Kurume 830, Japan.
AKASU,
Department
of
Physiology,
Kurume
University
School
of
Intracellular recordings were made from submucous plexus neurons of the guinea pig cecum maintained in vitro. Histamine (0.3-10 ~M) produced a dose-dependent membrane depolarization (=12 mV with 3 ~M) in about 26 % of the cells tested. Most of these showed a prominent calcium-activated potassium conductance (AH cells). Histamine-induced depolarization was less often observed in S cells (2 out of 33 cells) and the peak amplitude of the depolarization was less than 5 mV with i0 ~M. The depolarization was due primarily to an inactivation of potassium conductance which is available at the resting membrane potential of -60 mV. Peak amplitude of the fast excitatory postsynaptic potential (EPSP) was depressed by histamine (0.1-10 ~M) in a concentration-dependent manner (=65 % depression with 1 ~M). This was observed even in those cells where histamine did not produce any membrane depolarizations (mostly S cells). The depression of the fast EPSP resulted from presynaptic inhibition of acetylcholine (ACh) release, since membrane depolarizations produced by exogenously applied ACh were not significantly affected by histamine. Histamine-induced depression of ACh release was not affected by pretreatment of the preparation with hyoscine (100 nM) or idazoxan (i00 nM). This implied that histamine-induced depression of ACh release was not due to an activation of presynaptic muscarinic (M2) and adrenergic (~2) receptors. Histamine also reduced the amplitude of the non-cholinergfc, presumably pepti~ergic, slow EPSP by suppressing peptide release from the presynaptic nerve terminals. The peak amplitude of adrenergic inhibitory synaptic potentials was not depressed by histamine, suggesting that histamine receptors do not occur at presynaptic terminals of sympathetic nerve fibres. Both postsynaptic and presynaptic actions of histamine were blocked by cimetidine (I-30 ~M) or ranitidine (1-30 ~M) but not by pyrilamine (30 ~M), implying that receptors involved would be H 2 type.