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PubMed1999

Effects of Ca2+ concentration and Ca2+ channel blockers on noradrenaline release and purinergic neuroeffector transmission in rat tail artery.

1. The effects of Ca2+ concentration and Ca2+ channel blockers on noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves have been investigated in rat tail arteries in vitro. Intracellularly recorded excitatory junction potentials (e.j.ps) were used as a measure of ATP release and continuous amperometry was used to measure NA release. 2. Varying the extracellular Ca2+ concentration similarly affected the amplitudes of e.j.ps and NA-induced oxidation currents evoked by trains of ten stimuli at 1 Hz. 3. The N-type Ca2+ blocker, omega-conotoxin GVIA (omega-CTX GVIA, 0.1 microM) reduced the amplitudes of both e.j.ps (evoked by trains of ten stimuli at 1 Hz) and NA-induced oxidation currents (evoked by trains of ten stimuli at 1 Hz and 50 stimuli at 10 Hz) by about 90%. 4. The omega-CTX GVIA resistant e.j.ps and NA-induced oxidation currents evoked by trains of 50 stimuli at 10 Hz were abolished by the non-selective Ca2+ channel blocker, Cd2+ (0.1 mM), and were reduced by omega-conotoxin MVIIC (0.5 microM) and omega-agatoxin IVA (40 nM). 5. Nifedipine (10 microm) had no inhibitory effect on omega-CTX GVIA resistant e.j.ps and NA-induced oxidation currents. 6. Thus both varying Ca2+ concentration and applying Ca2+ channel blockers results in similar effects on NA and ATP release from postganglionic sympathetic nerves. These findings are consistent with the hypothesis that NA and ATP are co-released together from the sympathetic nerve terminals.

Adenosine Triphosphate↗
PubMed1967

The effect of intracellular current pulses in smooth muscle cells of the guinea pig vas deferens at rest and during transmission.

The effect of intracellular current pulses on the membrane of smooth muscle cells of the guinea pig vas deferens at rest and during transmission was studied. Two main response types were identified: active response cells, in which a spike was initiated in response to depolarizing currents of sufficient strength and duration; passive response cells, in which depolarizing currents gave only electrotonic potential changes. These cells were three times more numerous than the active response cells. During the crest of the active response the input resistance fell by about 25% of the resting value. Comparison of the active response with the action potential due to stimulating the hypogastric nerve showed that the former was smaller in amplitude and had a slower rate of rise and higher threshold. Electrical coupling occurred between the smooth muscle cells during the propagation of the action potential. Depolarizing current pulses had no effect on the amplitude of the excitatory junction potential (E.J.P.) in passive response cells, but in general did decrease its amplitude in active response cells. These results are discussed with respect to the mechanism of autonomic neuroeffector transmission.

Action Potentials↗
PubMed1995

Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway.

1. The effects of nitrosocysteine (cys-NO), L-N omega-nitroarginine (L-NNA) and L-N omega-nitro-L-arginine methylester (L-NAME), oxyhaemoglobin and Methylene Blue were observed on the resting membrane potential, muscle tone and excitatory junction potentials (EJPs) of cat tracheal smooth muscle tissue. 2. Cys-NO (10(-9) to 10(-6) M) showed no effect on the resting membrane potential of smooth muscle cells of the cat trachea but it dose-dependently relaxed the tracheal tissue in the presence of 5-HT, atropine and guanethidine. 3. Electrical field stimulation (EFS) applied during contraction evoked by 5-HT in the presence of atropine and guanethidine evoked non-adrenergic, non-cholinergic (NANC) muscle relaxation. L-NNA (10(-4) M) and L-NAME (10(-4) M) completely suppressed the relaxation when single or short repetitive stimuli were applied, but suppression was incomplete with repetitive stimuli of 4 ms pulse duration applied at 20 Hz. A substantial part of the L-NNA- or L-NAME-insensitive relaxation was abolished by tetrodotoxin. 4. Cys-NO dose-dependently suppressed the EJPs without changing the resting membrane potential, and L-NNA, L-NAME, Methylene Blue and oxyhaemoglobin enhanced the amplitude of the EJP to 1.2-1.5 times the control value. 5. EJPs showed some summation when repetitive field stimulation was applied at 20 Hz. L-NNA or L-NAME enhanced the summation, and the mean slopes were increased from 0.61 +/- 0.22 to 2.0 +/- 0.3, or 1.9 +/- 0.2 mV per stimulus. Vasoactive intestinal polypeptide (VIP) antiserum and VIP antagonists further enhanced the summation in the presence of L-NNA. 6. These results indicate that NANC relaxation can be classified into two different components according to the threshold for activation, and nitric oxide is involved in one. The present results also suggest that endogenous or exogenous nitric oxide has a prejunctional action in inhibiting excitatory neuroeffector transmission in addition to a direct action on the smooth muscle cells, presumably by suppressing transmitter release from the vagus nerve.

Animals↗
PubMed1985

Sonic motor pathways in teleost fishes: a comparative HRP study.

Among marine teleost fishes, one neuroeffector pathway for sonic communication consists of two components: a peripheral effector organ that consists of a swimbladder with associated 'drum' muscles, and a swimbladder or 'sonic' motor nucleus (SMN) located at the junction of the spinal cord and the medulla oblongata. Here, the organization of the SMN is compared in two unrelated groups of teleosts, the midshipmen, Porichthys notatus and P. myriaster, and the sea robin, Prionotus carolinus. Horseradish peroxidase (HRP), used as a retrograde tracer, revealed the position of the SMN in each species. While the SMN is a fused midline structure in midshipmen, it is bilateral in sea robins. The functional significance of these two contrasting patterns of organization remains to be explored. A third study group included mormyrid freshwater electric fish, which are also sonic. Mormyrids were included in part because an earlier study identified androgen-binding cells at a brain level comparable to that of the SMN of marine fishes. Using HRP methods, a swimbladder motor nucleus was identified at the caudal pole of the vagal motor column. However, the nucleus in mormyrids lies dorsal to the fourth ventricle and central canal, not ventral as it does in midshipmen and sea robins. Its position corresponds to the steroid-concentrating cells identified in a previous study.

Air Sacs↗
PubMed1985

Mechanism of alpha 2-adrenergic inhibition of neuroeffector transmission in the mouse vas deferens.

The process by which the activation of presynaptic alpha 2-adrenoceptors inhibits the release of noradrenaline from terminals of postganglionic sympathetic nerves was studied in the mouse isolated vas deferens. Clonidine was used as a prototypic agonist. Field stimulation-evoked excitatory junction potentials (e.j.p.s) were recorded from individual muscle cells. The e.j.p. amplitudes were taken as a measure of transmitter release. Changes in the external Ca2+ concentration from 2.5 to 1.25 or 5 mM caused corresponding changes in the size of e.j.p.s. When the normal Ca2+ concentration of the medium (2.5 mM) was substituted by equimolar quantities of Ba2+ or Sr2+, the e.j.p. amplitudes decreased considerably. Clonidine (0.3-30 nM) inhibited the nerve stimulation-evoked e.j.p. amplitudes in a concentration-dependent manner, without altering appreciably the frequency of spontaneous e.j.p.s. Procedures known to enhance Ca2+ entry into nerve terminals, like a high Ca2+ medium (Ca2+ 5 mM) or 4-aminopyridine 30 microM reduced the effect of clonidine. Repetitive nerve stimulation at 3 Hz, which is supposed to lead to an accumulation of free Ca2+ inside nerve terminals, similarly counteracted the effect of clonidine 10 nM. Whereas the alpha 2-adrenergic inhibition of the first e.j.p. in a train was unaffected, the inhibition of all successive e.j.p.s was gradually decreased. At 5 mM Ca2+ only the time-course of facilitation became faster, the decrease in alpha 2-adrenergic inhibition proceeded with the same pulse-dependent rate as at a normal external Ca2+ concentration, although from a lower initial level.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1988

Distinctive characteristics of the splenic vein in the dog. Its morphological and pharmacological discontinuities with the portal vein and splenic capsule.

Vascular characteristics of the splenic vein are entirely different from the portal vein in the dog. We compared the responsiveness of the splenic capsule, which contains abundant smooth muscle with the portal and splenic veins. With respect to potentiation of acetylcholine-induced contraction by neostigmine, the relaxation response to isoproterenol and the contractile response to 5-hydroxytryptamine, the splenic capsule differed from the splenic vein, but was rather similar to the portal vein. A site of morphological and pharmacological discontinuity between the portal vein and the splenic vein occurred at the junction of the splenic vein and the left gastric vein to form the gastrosplenic vein. This junction may coincide with the site of connection of the embryonic splenic vein, a newly formed efferent vein of the spleen, with the portal vein, which was reported by Miki [cf. Bevan et al.: 4th Int. Symp. on Vascular Neuroeffector Mechanisms; Raven Press, New York 1983]. On the splenic side, histological examination revealed that smooth muscle of the splenic capsule and trabeculae are interconnected, but did not extend to the splenic vein. At openings of the trabecular veins into the 'intrasplenic' portion of the splenic vein the trabecular smooth muscle continued to the extended capsule. The site of change in pharmacological responses was also found to be located between the trabeculae and the intrasplenic portion of the splenic vein. Thus the splenic vein can be regarded as a distinct segment of vessel inserted between the portal vein and the spleen. This may reflect differences in embryogenesis of their smooth muscle.

Animals↗
PubMed2000

Z-338, a newly synthetized carboxyamide derivative, stimulates gastric motility through enhancing the excitatory neurotransmission.

We studied the effects of Z-338, a newly synthesized carboxyamide derivative, on autonomic neuroeffector transmission in the guinea-pig stomach in relation to its gastrointestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338 (>10(-8) M) dose-dependently enhanced the amplitude of twitch-like contractions and excitatory junction potentials (EJPs) evoked by single or repetitive electrical field stimulation (EFS) without affecting the non-adrenergic non-cholinergic (NANC) relaxation and inhibitory junction potentials (IJPs) in the circular muscle strips of the guinea-pig stomach. Similar to the action of Z 338, pirenzepine (> 10(-8) M), a muscarinic M1-antagonist, enhanced the EJP amplitude, although AF-DX116 (M2-) and 4-DAMP (M3-antagonists) reduced the EJP amplitude, dose-dependently. The EC50 of the Z-338 and pirenzepine concentration response curves on EJPs were 4.7 x 10(-8) M and 1.0 x 10(-8) M, and Hill coefficients were 0.96 and 0.94 respectively. In addition, Z-338 slightly but significantly enhanced the amplitude of slow waves with or without initial spike. These results provide the first evidence that Z-338 exerts its gastrointestinal prokinetic action mainly through enhancing excitatory neuro effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.

Animals↗
PubMed1984

In vitro adrenergic and cholinergic innervation of the developing rat myocyte.

We studied the development of selective adrenergic and cholinergic neuroeffector transmission in primary cultures of isolated ventricular muscle cells. Explants of either thoracolumbar sympathetic ganglia or sacrococcygeal spinal cord were added to newborn rat ventricular cultures harvested prior to the onset of in vivo autonomic innervation. Neuronal growth, migration, and the formation of neuromuscular junctions were observed with light and scanning electron microscopy. Glyoxylic acid histofluorescence, reflecting catecholamine synthesis, was found in only the sympathetic neuromuscular cultures. Choline acetyltransferase activity was detected in both spinal cord and sympathetic neuromuscular cultures, but was significantly higher in the spinal cord neuromuscular cultures. The isolated ventricular muscle cells remained at a constant spontaneous contraction frequency, regardless of the type of culture preparation. Guanethidine sulfate application produced a positive chronotropic response, blocked by propranolol, in the sympathetic neuromuscular cultures, but not in the spinal cord neuromuscular cultures. Bethanechol sulfate produced a negative chronotropic response, blocked by atropine, in the spinal cord neuromuscular cultures, but not in the sympathetic neuromuscular cultures. Isolated ventricular muscle cells in the absence of neurons failed to respond to either agent. Direct microelectrode stimulation of adrenergic or cholinergic neurons likewise respectively produced either a positive or negative ventricular muscle cell chronotropic response. These studies are the first to establish the selective production of functional cholinergic and adrenergic innervation of isolated cardiac muscle cells in vitro.

Adrenergic Fibers↗
PubMed1977

Light and electron microscopic observations on noradrenergic nerves and striated muscle cells of the guinea pig urethra.

Neurohistochemical and electron microscopic techniques have been used to determine the arrangement and distribution of noradrenergic nerves and striated muscle in the wall of the guinea pig urethra. Fluorescent, catecholamine - containing nerves were observed among striated muscle cells only in the junctional zone between an inner layer of smooth muscle and an outer layer of striated cells. In this region considerable intermixing of the two types of muscle cell occurred. Electron microscopy has shown that noradrenergic terminal regions containing characteristic small dense-cored vesicles were invariable associated with smooth muscle cells; such nerves were never observed forming neuroeffector relationships with striated cells. These findings indicate that noradrenergic 'sympathetic' fibres are not directly involved in the functional control of urethral striated muscle.

Adrenergic Fibers↗
PubMed1986

Presynaptic opioid delta-receptors in the rabbit mesenteric artery.

Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation were recorded from muscle cells of the rabbit isolated mesenteric artery. At 0.03 Hz the e.j.p. amplitudes were stable. When a train of fifteen pulses was applied at 0.25 Hz or at higher frequencies (0.5, 1 and 2 Hz), e.j.p.s showed an initial facilitation followed by depression. [Met5]enkephalin 0.1 and 1 mumol/l, [D-Ala2,D-Leu5]enkephalin 0.1 and 1, but not 0.01 mumol/l, and [D-Pen2, L-Pen5]enkephalin 3 mumol/l all depressed the e.j.p.s evoked by trains of fifteen pulses at 1 Hz. When more than one concentration was used ([Met5]enkephalin, [D-Ala2,D-Leu5]enkephalin), the inhibition was concentration dependent. It was always greater for the first few e.j.p.s than for the later ones in a train. [Met5]enkephalin 1 mumol/l reduced the first e.j.p. at 1 Hz and the e.j.p.s evoked by 0.03 Hz to a similar extent. The inhibitory effect of [Met5]enkephalin 1 mumol/l on e.j.p.s persisted in the presence of yohimbine 0.3 mumol/l. Naloxone 1 mumol/l did not interfere with the effect of [Met5]enkephalin 1 mumol/l. Naloxone 10 mumol/l depressed some e.j.p.s and prevented the inhibition by [Met5]enkephalin 1 mumol/l. Neither ICI 154129 10 mumol/l nor ICI 174864 0.3 mumol/l had any effect of their own and both compounds antagonized the action of [Met5]enkephalin 1 mumol/l. Normorphine 10 mumol/l, fentanyl 1 mumol/l, ethylketocyclazocine 0.1 mumol/l, and dynorphin A(1-13) 1 mumol/l were all ineffective. Ethylketocyclazocine 1 mumol/l did not change the e.j.p.s either, but antagonized [Met5]enkephalin 1 mumol/l. [Met5]enkephalin 1 mumol/l failed to influence both the resting membrane potential of the muscle cells and the depolarizing effect of noradrenaline 3 and 30 mumol/l. We suggest that the axon terminals of post-ganglionic sympathetic neurones in the rabbit mesenteric artery possess opioid delta-, but not mu- or kappa-receptors. The activation of presynaptic delta-receptors inhibits the release of the neuroeffector transmitter. There is no evidence for any effect of co-released endogenous opioid peptides under our experimental conditions.

Action Potentials↗
PubMed1978

Control of the salivary glands of Helisoma by identified neurones.

The neural regulation of an exocrine gland was investigated at the level of identified effector neurones. The salivary gland neuroeffector system of Helisoma consists of a pair of acinous glands innervated by two symmetrically located, identified buccal ganglion neurones (4R and 4L). Neurones 4R and 4L usually are electrically coupled and display synchronous activity. Action potentials in these neurones elicit EPSPs and action potentials in epithelial cells of the salivary glands. Spontaneous miniature potentials similar to those seen at neuromuscular junctions can be recorded from many of the glandular cells. Neurones 4R and rL, and thus also salivary gland cells, can display bursts of action potentials phase-locked with those seen in buccal mass motoneurones during feeding.

Action Potentials↗
PubMed1978

Effects of prostaglandin E2 and a prostaglandin endoperoxide analogue on neuroeffector transmission in the rat anococcygeus msucle.

1 Investigations were made into the effects of prostaglandin E(2) (PGE(2)) and a prostaglandin endoperoxide analogue (Upjohn compound U-46619) on the responses of the rat anococcygeus muscle to field stimulation of the intrinsic sympathetic nerves, and to exogenous noradrenaline. The effects of PGE(2) on responses to stimulation of intrinsic inhibitory nerves were also studied.2 PGE(2) (5.6 x 10(-8) or 2.8 x 10(-6) mol/l) decreased motor (sympathetic) responses to field stimulation at all frequencies tested (2 to 24 Hz). The prostaglandin also reduced the inhibitory responses to field stimulation, seen when the tone of the preparation had been raised and its sympathetic innervation had been blocked by guanethidine. However, these inhibitory responses were also reduced by other spasmogens (carbachol and 5-hydroxytryptamine) which, like PGE(2), further increased the tone of guanethidine-treated preparations.3 At a concentration of 5.6 x 10(-8) mol/l, PGE(2) had no effect on responses to noradrenaline, whereas at a fifty-fold higher concentration the prostaglandin potentiated these.4 Unlike PGE(2), U-46619 (5.6 x 10(-8) mol/l) greatly potentiated motor responses to field stimulation, at frequencies from 0.75 to 24 Hz. This effect did not represent a specific facilitation of sympathetic neurotransmission, as responses to carbachol and 5-hydroxytryptamine, as well as to noradrenaline, were also potentiated.5 The results are discussed in relation to the effects of prostaglandins and prostaglandin endoperoxides on neuroeffector transmission in other sympathetically innervated tissues. It is concluded that PGE(2) inhibits sympathetic neurotransmission in the rat anococcygenus muscle by a prejunctional action, whereas the predominant effect of U-46619 is direct excitation of the muscle. The effect of PGE(2) on inhibitory responses to field stimulation may represent an interference with inhibitory neuroeffector transmission in this tissue, or may simply be a consequence of the spasmogenic action of the prostaglandin.

Animals↗
PubMed1979

Some bases of differences in vascular response to sympathetic activity.

Basic patterns of neuroeffector organization vary widely in the vasculature, in general, with vessel diameter and type, and confer distinctive properties. The smaller the vessel, the more intimate the neuroeffector relationship, the more localized the action of the released transmitter, and the more important myogenic conduction compared to transmitter diffusion for the coordination of vascular effector response. Seemingly superimposed upon these basic general patterns are other variable features, conferring upon vessels of similar size and type diversity of function. These variables include sensitivity and magnitude and possible location of alpha- and beta-receptors and their subtypes, presence and nature of intrinsic vascular tone, and the density and pattern of adrenergic innervation to mention the more important. Functional diversity in neuroeffector characteristics can, to some extent, be understood in relation to embryological development, neurotrophic influences, effector regulation of innervation, and the mural response to an increase in intravascular pressure.

Animals↗
PubMed1990

A comparison of the actions of cromakalim and nifedipine on rabbit isolated mesenteric artery.

This study shows that cromakalim (0.4-10 microM) can concentration-dependently hyperpolarize the smooth muscle cell membrane and increase 86Rb efflux from rabbit mesenteric small arteries at concentrations which inhibit noradrenaline-induced increases in perfusion pressure in this preparation. Hyperpolarisation of the cell membrane by cromakalim was inhibited by prior exposure of the tissue to glibenclamide (1 microM). Noradrenaline (greater than 1 microM) depolarized the smooth muscle cell membrane and this effect was reduced in the presence of cromakalim. Experiments involving repetitive stimulation of the perivascular nerves in this tissue showed that cromakalim (2-10 microM) reduced excitatory junction potential amplitude and fall time without affecting the facilitation process. The results of this study suggest that in rabbit small mesenteric arteries the vasodilator action of cromakalim is a consequence of the opening of 86Rb-permeable potassium channels. It is unlikely that any component of the vasorelaxant effects of cromakalim is due to a direct effect on voltage-operated calcium channels or a prejunctional effect on neuroeffector transmission.

Animals↗
PubMed1990

Effects of azelastine on vagal neuroeffector transmission in canine and human airway smooth muscle.

Azelastine is a newly developed antiallergic drug that is reported to antagonize histamine and leukotrienes in addition to its inhibitory action on release of chemical mediators. In the present study, the effects of azelastine on neuroeffector transmission in the airway smooth muscles with double sucrose gap and isometric tension-recording methods were evaluated. Azelastine (10(-8) to 10(-6) mol/L) markedly decreased the contractile response of human bronchial and dog tracheal muscle strips to electrical field stimulation (10 pulses at 20 V, 20 Hz, 800 microseconds) in a dose-dependent manner. In parallel with actions on twitch contractions, azelastine suppressed the amplitude of excitatory junction potentials of dog trachea without changing the resting membrane potential and input resistance of smooth muscle cells. However, azelastine did not alter acetylcholine sensitivity of the smooth muscle cells. These results indicate that azelastine possesses an inhibitory action on the release of acetylcholine by vagal nerve terminals. This inhibitory effect of azelastine may contribute to the treatment of asthma in addition to its antiallergic actions.

Acetylcholine↗
PubMed1984

Autonomic neuroeffector mechanisms in smooth muscle.

While the classical view is that the autonomic nervous system consists largely of antagonistic cholinergic and adrenergic nerves, about sixteen putative neurotransmitters in the autonomic nervous system have been proposed in the past few years, including various monoamines, polypeptides, purines and amino acids. Modulatory transmitter mechanisms have also been recognised, including prejunctional inhibition or enhancement of transmitter release, postjunctional modulation of transmitter action, and the secondary involvement of locally synthesised hormones and prostaglandins. The existence of more than one transmitter substance in some nerves is now widely recognised, and suggestions are made about the ways that this can lead to further peripheral control mechanisms at nerve terminals themselves. The cotransmitters always have synergistic actions on postjunctional effector cells, but two different mechanisms are postulated. (1) If both substances are stored in the same vesicles (for example, ACh or NA with ATP), release is closely parallel at all impulse frequencies. Upon release, the cotransmitter, in addition to having a direct action on postjunctional cells, may facilitate the action of the other transmitter and/or act as an inhibitor of its release. (2) If the two substances are stored in separate and different vesicle types (for example ACh or NA with some peptides), then differential release is possible at different impulse frequencies; the peptides released at higher frequencies modulate the role of the classical transmitters, by both prejunctional enhancement of its release and postjunctional facilitation of its action. The long-term effects by 'trophic' factors released by excitable cells including NGF, purine nucleosides and polypeptides, on development and regeneration were considered. The part played by peripheral neuroeffector control mechanisms has been underestimated. These are additional to central and ganglionic control mechanisms and are much more elaborate than originally thought.

Acetylcholine↗
PubMed1991

Effects of vasoactive intestinal polypeptide antagonists on cholinergic neurotransmission in dog and cat trachea.

1. The effects of vasoactive intestinal polypeptide (VIP) antagonists [AC-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were investigated by use of microelectrode, double sucrose-gap and tension recording methods. 2. In the dog trachea, repetitive stimuli at high frequency (20 Hz) markedly enhanced the amplitude of contraction, the amplitude of contractions evoked by 50 stimuli at 20 Hz relative to that evoked by 5 stimuli being 14.2 +/- 3.8 times (n = 7, +/- s.d.). In the cat, the summation was much less marked, the amplitude of contractions evoked by 50 stimuli relative to that evoked by 5 stimuli being only 2.1 +/- 0.6 times (n = 5, +/- s.d.). Neither VIP antagonist had any effect on the relationship between the number of stimuli at 20 Hz and the relative amplitude of contraction in the dog trachea, but did enhance the amplitude of contractions to 1.1-1.5 times control in the cat trachea. 3. VIP antagonists dose-dependently enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single stimulus in the cat trachea, without changing the resting membrane potential or input membrane resistance of the smooth muscle cells. However, neither antagonist had any effect on the amplitude of the e.j.p. in the dog trachea. 4. Neither VIP antagonist had any effect on the post-junctional response of smooth muscle cells to exogenously applied acetylcholine (ACh; 10(-9)-10(-5) M) in the dog or cat trachea.5. In the cat trachea, VIP (10-11 M) suppressed the ej.p. amplitude to 0.74 +/- 0.09 times the control value (n = 6). However, after pretreatment of the tissue with the VIP antagonists [Ac-Tyr', D-Phe2]-GRF(1-29)- H2 (10-8M) and [4-Cl-D-Phe6, Leu17]-VIP (10-8M), VIP (10-11 M) did not suppress the ej.p. amplitude, indicating that VIP antagonists block the presynaptic inhibitory action of exogenous VIP.6. In parallel with the enhancement of contraction, ej.ps showed marked summation when repetitive field stimulations were applied at high frequency (20 Hz) in the dog trachea. The relationship between the relative amplitude of the ej.p. and number of stimuli at 20 Hz was linear and the slope was 2.2 +/- 0.3 mV/stimulation. VIP antagonists did not affect this relationship. However, in the cat trachea, summation of ej.ps was not at all marked and a linear relationship was not observed with the double sucrose-gap method. Incubation of the cat tracheal tissue with either of the VIP antagonists (10-8 or 10-7M) markedly enhanced the summation of ej.ps evoked by repetitive field stimulation at 20 Hz, and after the treatment a linear relationship between the number of stimuli and the amplitude of ej.ps was observed, the slopes being 0.6 +/- 0.1 (n = 8) and 0.55 +/- 0.1 mV/stimulation (n = 5), respectively.7. These results indicate that both VIP antagonists, [Ac-Tyr', D-Phe2]-GRF(1-29)-NH2 and [4-Cl-DPhe6, Leu17]-VIP, have a prejunctional action accelerating the excitatory neuroeffector transmission, presumably by enhancing transmitter release from the vagus nerves in the cat, but not in the dog trachea.

Acetylcholine↗