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Biomedical subjects

M W McCulloch

Publications and source records attributed to M W McCulloch.

At least 37 records · Page 2Linked to original sources
PubMed1978

Modulation of noradrenergic transmission in the rabbit ear artery by dopamine.

1. The effects of dopamine on vasoconstrictor responses to field stimulation of sympathetic nerves and to exogenous noradrenaline were studied in the isolated ear artery of the rabbit. Responses to noradrenaline were unchanged at the start of the dopamine infusions but were enhanced as the infusions continued and also after cessation of the infustion. 2 Dopamine (0.5 muM) reduced the stimulation-induced efflux of tritium from segments of ear artery labelled with [3H]-noradrenaline. The reduction persisted during 65 min of dopamine infusion, after which time the vasoconstrictor responses had generally recovered to 93% of control level. On ceasing the infusion, the stimulation-induced efflux and the vasoconstrictor responses were enhanced. 3 Metoclopramide, haloperidol and ergometrine, each in a concentration of 0.2 muM, prevented the inhibitory effect of 0.5 muM dopamine on the stimulation-induced tritium release, but not the inhibitory effect of 0.5 muM noradrenaline. Phenoxybenzamine (0.2 and 1 muM) and phentolamine (1 muM) prevented the inhibitory effects of both noradrenaline and dopamine on the stimulation-induced efflux, and phentolamine (0.2 muM) prevented the inhibition of the stimulation-induced release by noradrenaline but only partially prevented the inhibitory effect of dopamine on the stimulation-induced efflux. 4 A possible role for dopamine in the modulation of noradrenergic transmission is suggested.

Animals↗
PubMed1977

Effects of pimozide on noradrenergic transmission in rabbit isolated ear arteries.

In the rabbit ear artery both dopamine and noradrenaline inhibit stimulation-induced (S-I) transmitter noradrenaline efflux. Pimozide, which is reported to be a specific dopamine receptor antagonist, was used to further study the effects of dopamine on transmitter efflux. In a concentration of 0.2 micrometer pimozide blocked the inhibition of S-I efflux produced by 0.5 micrometer dopamine but not that produced by 0.5 micrometer noradrenaline. In a concentration of 10 nM, pimozide enhances transmitter release and vasoconstrictor responses to sympathetic nerve stimulation; this may be due to blockade of feedback inhibition of transmitter release by endogenous dopamine. In a concentration of 1 micrometer, pimozide reduced transmitter release and vasoconstrictor responses to sympathetic nerve stimulation. Vasoconstrictor responses to noradrenaline and histamine are antagonized by pimozide in a noncompetitive manner.

Animals↗
PubMed1976

Effects of beta-adrenoreceptor blocking drugs on adrenergic transmission.

The peripheral actions of beta-adrenoreceptor antagonists on adrenergic transmitter mechanisms have been reviewed. In addition to receptor blockade, beta-adrenoreceptor antagonists may in high concentrations inhibit neuronal uptake of noradrenaline; inhibit monoamine oxidase; inhibit the uptake of noradrenaline into transmitter storage vesicles and inhibit the extraneuronal uptake of noradrenaline. High concentrations of beta-adrenoreceptor antagonists (threshold about 30 muM) also release noradrenaline from intraneuronal stores; however, their intrinsic sympathomimetic activity is generally attributed to their partial agonist property. Beta-adrenoreceptor antagonists possess adrenergic neurone blocking activity and quinidine-like or local anaesthetic activity. The existance of a positive feedback mechanism involving prejunctional beta-adrenoreceptors is discussed. It is suggested that bradycardia produced by beta-adrenoreceptor antagonists is due to blockade of the action of circulating catecholamines or of transmitter noradrenaline at cardiac extrajunctional beta-adrenoreceptor sites.

Adrenergic beta-Antagonists↗
PubMed1975

Modulation by acetylcholine of adrenergic transmission in the rabbit ear artery.

1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission.

Acetylcholine↗
PubMed1975

Effects of phenoxybenzamine and norepinephrine on transmitter release in the pulmonary artery of the rabbit.

The effects of phenoxybenzamine and norepinephrine (NE) on the release of tritiated NE were studied in spiral strips of the rabbit pulmonary artery. Phenoxybenzamine increased the tritiated NE efflux induced by transmural stimulation at 4 Hz by a factor of three. The magnitude of this effect was inversely related to the frequency of stimulation. NE (2.5 times 10- minus 6 M) decreased the enhancing effect of short exposure but not long exposure to phenoxybenzamine, probably by surmounting the phenoxybenzamine blockade of the alpha-adrenergic receptors on the adrenergic nerve terminal. The transmitter output per pulse increased with the frequency from 4 to 16 HZ and decreased at 32 HZ. This evidence suggests that a negative feedback mechanism does operate in this vascular preparation but, probably because of the wide neuromuscular cleft, is less effective than in tissues with a narrower synaptic interval.

Animals↗
PubMed1972

Antagonism of noradrenaline and histamine by desipramine in the isolated artery of the rabbit ear.

1. The effects of desipramine (DMI) were examined on the vasoconstrictor responses of the isolated perfused artery of the rabbit ear to noradrenaline (NA) and to histamine. Innervated and sympathetically denervated arteries were used.2. In innervated arteries, DMI in concentrations of 1 x 10(-8) to 1 x 10(-7)M enhanced the responses to NA; higher concentrations reduced the responses. In sympathetically denervated arteries, DMI caused only reduction of the responses to NA.3. Responses to histamine were reduced by DMI in both innervated and denervated arteries. DMI was considerably more potent as an antagonist of histamine than of noradrenaline.4. The reduction by DMI of the responses to NA and histamine in both innervated and denervated arteries was associated with a parallel shift to the right of the concentration-response curves of the agonist and a depression of the maximal response. These effects of DMI were reversible.5. Analysis of the data by the method of Arunlakshana & Schild (1959) showed the following: the antagonism of the action of NA by DMI on denervated arteries fulfilled the requirements for competitive antagonism; antagonism of the action of NA on innervated arteries was not competitive; antagonism of the actions of histamine on innervated and denervated arteries was not competitive.6. It is suggested that DMI antagonizes the action of NA and histamine on the perfused artery of the rabbit ear in two ways: (i) reversible specific antagonism which is competitive for NA and not competitive for histamine; (ii) reversible non-specific antagonism which is non-competitive for both agonists.

Animals↗
PubMed1972

Factors affecting the extraneuronal inactivation of noradrenaline in cardiac and smooth muscle.

1. The relation between density of adrenergic innervation, noradrenaline (NA) accumulation (as seen with the fluorescence histochemical method) in tissues incubated in a high concentration of NA, and monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activities, were examined in a wide range of tissues from different species.2. Evidence was obtained to support the proposal that accumulation of NA in the non-innervated smooth muscle of the human umbilical artery and chick amnion is associated with very low activities of COMT within muscle cells.3. The wide variation in tissue accumulation of NA in adrenergically innervated muscles was confirmed. For example, in the rabbit atrium and rat vas deferens, there was high NA accumulation in vascular smooth muscle but not in other muscle cells. In the mouse vas deferens there appeared to be preferential NA accumulation in the outer longitudinal muscle in comparison with the circular muscle. In the ventricle of the rat and mouse individual muscle cells showed different degrees of accumulation of NA. Many unidentified fluorescent cells were revealed in the submucosa of the guinea-pig ureter following loading with NA. The highest activities of COMT were found in the rat vas deferens and the lowest in the rabbit vascular tissues; the highest activity of MAO was found in the guinea-pig ileum, and the lowest in the rat aorta.4. No simple relation between tissue activities of MAO and COMT and degree of NA accumulation was found. Possible directions for further investigation of the problem are discussed.

Amnion↗
PubMed1969

Mechanism of the antagonism between guanethidine and dexamphetamine.

1. The effects of dexamphetamine were studied on the responses of rabbit ileum, rabbit ear artery and sheep spleen to sympathetic nerve stimulation after exposure to guanethidine and in the absence of guanethidine.2. In the absence of guanethidine, dexamphetamine enhanced the responses to sympathetic stimulation and, in the spleen, this was shown to be due to an increase in noradrenaline output. However, the increase in these responses was much less than the increase obtained in preparations treated with guanethidine.3. Cocaine, in a concentration which produced the same effect on noradrenaline uptake as the concentration of dexamphetamine used, was also effective in reversing the adrenergic neurone blocking actions of guanethidine.4. It is suggested that the antagonism between dexamphetamine and guanethidine is due to a reduction in the uptake of guanethidine by the nerve endings rather than to interaction of the two drugs at the receptor site for the adrenergic neurone blocking action of guanethidine.

Animals↗