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G BROWNLEE

Publications and source records attributed to G BROWNLEE.

14 recordsLinked to original sources
PubMed1963

THE SITE OF THE 5-HYDROXYTRYPTAMINE RECEPTOR ON THE INTRAMURAL NERVOUS PLEXUS OF THE GUINEA-PIG ISOLATED ILEUM.

Dose/response measurements were made on the guinea-pig isolated ileum with six agonists, acetylcholine, 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium, choline phenyl ether and histamine. The dose effects were repeated in the presence of each of twelve antagonists and one anticholinesterase. Acetylcholine and histamine were chosen because of their direct mode of action on smooth muscle, nicotine, dimethylphenylpiperazinium and choline phenyl ether were used as examples of drugs that act at the ganglionic acetylcholine receptor. 5-Hydroxytryptamine was the drug investigated. Hyoscine blocked the contractions caused by acetylcholine, 5-hydroxytryptamine and the ganglion-stimulants but left the responses to histamine unchanged. The anticholinesterase N,N'-diisopropylphosphorodiamidic fluoride (mipafox) potentiated all the agonists except histamine. The strength of potentiation decreased in the order 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether, and acetylcholine. The local anaesthetic procaine inhibited to the same extent contractions elicited by 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether. These results showed that 5-hydroxytryptamine, like nicotine, choline phenyl ether and dimethylphenylpiperazinium, mediated its response through the nervous plexus. Of those tested 5-hydroxytryptamine was the only specific antagonist to 5-hydroxytryptamine; lysergic acid derivatives produced spasm and prolonged changes in tone; phenoxybenzamine caused non-specific block. The diverse modes of action of a number of ganglion-blocking agents were selectively used. Thus hexamethonium, pentolinium, and nicotine in its competitive phase, blocked contractions due to nicotine, dimethylphenylpiperazinium and choline phenyl ether and left those due to 5-hydroxytryptamine, acetylcholine and histamine unchanged. The depolarizing ganglion-blocking agents, dimethylphenylpiperazinium and nicotine, inhibited the responses to all the indirectly acting drugs. Furthermore, mecamylamine, a drug with a less well-defined mode of action, partially inhibited contractions due to 5-hydroxytryptamine in a concentration that blocked those due to nicotine, dimethylphenylpiperazinium and choline phenyl ether. Pempidine, known to act like mecamylamine, did not antagonize 5-hydroxytryptamine. It is concluded that 5-hydroxytryptamine activates specific receptors sited at the intramural parasympathetic ganglion cells.

Acetylcholine↗
PubMed1963

SOME PHARMACOLOGICAL PROPERTIES OF THE CIRCULAR AND LONGITUDINAL MUSCLE STRIPS FROM THE GUINEA-PIG ISOLATED ILEUM.

A circular and a longitudinal muscle strip were prepared from adjacent parts of a guinea-pig ileum and a direct pharmacological comparison made under identical conditions. The longitudinal preparation was sensitive to acetylcholine, methacholine, carbachol, 5-hydroxytryptamine, histamine and nicotine, while the circular preparation was insensitive to 5-hydroxytryptamine, histamine and nicotine, and responded to the choline esters only in high concentrations. Incubation of the preparations with the anticholinesterase, mipafox (NN-diisopropylphosphodiamidic fluoride), sensitized both preparations to the action of acetylcholine; potentiation of the contraction of the longitudinal muscle was 16-times; that of the circular one 4,000-times. The longitudinal muscle was more sensitive than the circular muscle to acetylcholine whether both were treated with mipafox or not. Bradykinin and substance P both stimulated the longitudinal but not the circular muscle, an effect not modified after mipafox. Hyoscine antagonized the responses of the circular muscle strip, treated with mipafox, to acetylcholine and to histamine, but on the longitudinal muscle strip the response to histamine was not affected, the response to acetylcholine being competitively antagonized. Morphine, in the same concentrations on both circular and longitudinal muscle strips, antagonized the stimulant actions of nicotine and to a lesser extent of 5-hydroxytryptamine, but the responses to histamine on the longitudinal muscle strip were not antagonized by morphine which was in contrast to its action on the circular muscle strip. These observations showed that the main differences in the responses of the circular and longitudinal muscle of the guinea-pig ileum to drugs were in the intrinsic properties of the smooth muscle cells. In addition cholinesterase may protect the circular muscle cells. Finally the circular muscle strip preparation proved to be a useful tool to study the action of drugs on the nervous plexuses of the ileum of the guinea-pig.

Acetylcholine↗
PubMed1953

Polymyxin.

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Anti-Bacterial Agents↗