Short‐term desensitization of guinea‐pig taenia caecum induced by carbachol occurs at intracellular Ca stores and that by histamine at H1‐receptors

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Abstract
In Ca‐free solution, the contractile response of guinea‐pig taenia caecum to 10−4 m carbachol was mediated through muscarinic receptors and was reduced time‐dependently by desensitization with 10−4 m carbachol, but not 10−4 m histamine. On the other hand, the response to 10−4 m histamine was shown to be mediated through H1‐receptors and to be reduced time‐dependently by desensitization with either 10−4 m histamine or 10−4 m carbachol. The maximal K+ contraction was not changed by desensitization with carbachol or histamine. Thus, contractile proteins and voltage‐dependent Ca channels maintain their normal functions. To study the coupling of Ca channel activity in cell surface membrane to receptor activation, the contractile responses elicited by carbachol and histamine added simultaneously with Ca to Ca‐free solution were measured. The response elicited by carbachol plus Ca was not changed by desensitization with carbachol, while that elicited by histamine plus Ca was reduced by desensitization with histamine. These results show that desensitization by carbachol occurs at a post‐receptor site, whereas that induced by histamine occurs at H1‐receptors. After desensitization with carbachol, but not histamine, the contractile response to 5 × 10−2 m caffeine in Ca‐free solution was significantly reduced. These results show that short‐term desensitization of guinea‐pig taenia caecum by carbachol is heterologous and occurs at intracellular Ca stores, while that induced by histamine is homologous and occurs at histamine H1‐receptors.

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