Evaluation of Agents That Release or Modify Release of Adrenergic Transmitter

Armstrong, J M; Green, A. F.

doi:10.1007/978-3-642-67505-8_4

Cited by 7 publications

(3 citation statements)

References 221 publications

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“…1) In the sympathetic nervous system, it is generally considered that the stimulation of nerve fibres induces not only a release of noradrenaline but also a release of PGE series (Chanh, Junstad & Wennmalm, 1972;Hedqvist, 1976). However, no consensus has been obtained as to whether endogenous prostaglandins play a role in regulation of transmitter release from nerve terminals (see for example, Armstrong & Green, 1980). In order to establish a physiological role for endogenous prostaglandin, it is important to show the effects of a prostaglandin synthesis inhibitor or a prostaglandin antagonist on a physiological response.…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin‐induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.

Inoue¹,

Ito²,

Takeda³

1984

The Journal of Physiology

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In an attempt to elucidate the possible roles of endogenous prostaglandins on the neuro‐effector transmission in the dog trachea, effects of a prostaglandin antagonist (1‐acetyl‐2‐[8‐chloro‐10, 11‐ dihydrobenz (b.f) (1.4) oxazepine‐10‐carbonyl]hydrazine (SC‐19220] on the electrical and mechanical properties of smooth muscle cells and on neuro‐effector transmission in the smooth muscle layer were studied by means of micro‐electrode, double sucrose‐gap, and tension recording methods. The levels of prostaglandins in the perfusate from the dog tracheal tissue were also determined using radioimmunoassay. Excitatory junction potentials (e.j.p.s) and twitch tension evoked by electrical field stimulation with short pulse duration (50‐100 microseconds), which were abolished by tetrodotoxin (10(‐7) M) or atropine (5 X 10(‐6) M), showed gradual and continuous reduction in amplitude during superfusion with normal Krebs solution. Reduction in the amplitude of e.j.p.s occurred with no change in the membrane potential or membrane input resistance. SC‐19220 (3.1 X 10(‐5) M) did not modify the membrane potential, membrane input resistance or the sensitivity to acetylcholine of the smooth muscle cells. Yet, with application of SC‐19220 (3.1 X 10(‐6) M), gradual and continuous reductions in the amplitude of e.j.p.s and twitch contractions were no longer observed. With an increased concentration (3.1 X 10(‐5) M), e.j.p.s and twitch contractions with a constant amplitude were obtained after the initial increase in the amplitude. When the amplitude of twitch contractions was stabilized by treatment with indomethacin (10(‐5) M), low concentrations (10(‐12) to 10(‐10) M) of prostaglandin E2 (PGE2) or prostaglandin F2 alpha (10(‐8) to 10(‐6) M) markedly suppressed the amplitude of the twitch contractions. In some muscle preparations (ten out of twenty‐two preparations examined), SC‐19220 (3.1 X 10(‐6) to 3.1 X 10(‐5) M) produced a sustained contraction of the muscle, which was suppressed by atropine (5 X 10(‐6) M) or PGE2 (10(‐8) M). Following pre‐treatment of the tissue with atropine (5 X 10(‐6) M), SC‐19220 did not evoke contracture. In the resting condition, 10‐40 ng g‐1 wet wt. tissue min‐1 PGE or PGF was released into the perfusate from the tracheal muscle tissue of the control dog.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Resultsmentioning

confidence: 99%

Prostaglandin‐induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.

Inoue¹,

Ito²,

Takeda³

1984

The Journal of Physiology

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“…a physiological role in attenuating both the release of the transmitter and its effects on adrenergic neuromuscular transmission (Hedqvist, 1969(Hedqvist, , 1976Langer, 1977;Westfall, 1977;Gillespie, 1980;Armstrong & Green, 1980;Needleman & Isakson, 1980). However, no consensus was obtained as to whether endogenous PGs play a role in suppression of the release of chemical transmitter or whether these PGs modulate the release of transmitters from nerve terminals, e.g.…”

Section: Introductionmentioning

confidence: 99%

Modulation of neuromuscular transmission by endogenous and exogenous prostaglandins in the guinea‐pig mesenteric artery

Kuriyama

Makita

1982

The Journal of Physiology

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1. At concentrations of 2·8 × 10−8‐2·8 × 10−6 M, prostaglandins (PGs; PGE1, PGE2 and PGF2α) had no effect on membrane potential and resistance of smooth muscles of the guinea‐pig mesenteric artery. PGs (2·8 × 10−8 M) suppressed the contraction evoked by perivascular nerve stimulation, but did not suppress the contraction evoked by direct muscle stimulation. 2. PGs (2·8 × 10−8 M) suppressed the e.j.p.s evoked by repetitive perivascular nerve stimulation but preserved the facilitation process of e.j.p.s evoked by any given stimulus frequency (0·1‐1·0 Hz). 3. The relationships between e.j.p. amplitudes and [Ca]o plotted on log scales in the presence or absence of PGE2 were not parallel. High concentrations of [Ca]o prevented the inhibitory actions of PGs on the amplitude of e.j.p.s. 4. PGE2 did not suppress the activity of nerve fibres contributing to the generation of e.j.p. 5. Indomethacin (10−6 M) enhanced the amplitude of e.j.p.s and the frequency of miniature e.j.p.s with no change in the membrane potential and resistance of smooth muscles; these actions of indomethacin were suppressed by PGE2 (2·8 × 10−8 M). 6. Phentolamine (10−7 M) enlarged and yohimbine (10−7 M) reduced the amplitude of the first e.j.p. evoked by a train stimulation, but the maximum amplitude of e.j.p., after the facilitation was completed, was in both cases much larger than that observed in the control. The enhancement of the transmission process was also suppressed by PGs (2·8 × 10−8 M). 7. The results indicate that in the guinea‐pig mesenteric artery, PGs mainly suppress chemical transmitter release from nerve terminals due to interactions with Ca influx, but not due to interaction with presynaptic α‐adrenoceptors. Endogenous PG may act as a regulator substance in neuromuscular transmission.

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“…The route of discovery of guanethidine was entirely separate and the pharmacological methods used by Dr R.A. Maxwell and his colleagues were different. However, the similarities between the two compounds became increasingly clear as pharmacological investigations proceeded (for reviews Green 1962;Boura & Green, 1965;Maxwell & Wastila, 1977;Armstrong & Green, 1980). However, two major distinctions remain, both of which we took into consideration at the Wellcome Laboratories when in the early 1960s we sought a better adrenergic neurone blocking agent than either bretylium or guanethidine.…”

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confidence: 99%

The discovery of bretylium and bethanidine.

Af¹

1982

Brit J Clinical Pharma

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Evaluation of Agents That Release or Modify Release of Adrenergic Transmitter

Cited by 7 publications

References 221 publications

Prostaglandin‐induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.

Prostaglandin‐induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue.

Modulation of neuromuscular transmission by endogenous and exogenous prostaglandins in the guinea‐pig mesenteric artery

The discovery of bretylium and bethanidine.

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