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Department of Pharmacology, St. George's Hospital Medical School, London SW17 0RE

1. Shortening and rate of loss of ⁴²K were studied in strips of longitudinal muscle taken from guinea-pig ileum.

2. Carbachol, histamine and raising the external potassium concentration, [K⁺]_o, to 120 mM in the presence of atropine caused equal maximal shortenings of the muscle, but unequal maximal increases in ⁴²K efflux: maximal ⁴²K effluxes obtainable in response to raised [K⁺]_o and histamine were about and respectively of the maximal efflux in response to carbachol. In the absence of atropine the increase in ⁴²K efflux produced by 120 mM-[K⁺]_o was about 50% larger, probably because of the release of acetylcholine from nerve endings in the tissue.

3. If inhibitors of histamine metabolism were applied, or a H₂-receptor blocker (cimetidine), the maximum ⁴²K efflux produced by histamine was not increased. An analogue of histamine reputed to resist metabolic degradation did not produce a larger increase in ⁴²K efflux than histamine. The smaller maximal effect of histamine on ⁴²K efflux than carbachol may be because it can open fewer ion channels in the smooth muscle membrane.

4. The ratio of the concentrations producing 50% maximal shortening and 50% maximal ⁴²K efflux was about 1:1.3 for raised [K⁺]_o but about 1:20 for histamine and carbachol. Depolarization by raising [K⁺]_o appears to be less effective in causing tension development than similar depolarizations produced by carbachol or histamine.

5. The relative effects of carbachol, histamine and raised [K⁺]_o were discussed in the light of their similar depolarizing actions. Increases in ⁴²K efflux did not appear to be caused primarily either by contraction or by depolarization of the muscle. Access of the stimulant to cells and receptors other than those which are superficially situated was suggested as being an important factor in deciding the smaller increase in ⁴²K efflux seen with some stimulants. Histamine receptors may be fewer in number than muscarinic receptors and less able in their activated form to open channels through which potassium ions can escape.

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