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

Abstract

1 In Ca-free solution, the contractile response of guinea-pig taenia caecum to 1O-'M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 1O-4M carbachol, but not 1O-4M histamine. On the other hand, the response to 1O-4M histamine was shown to be mediated through HI-receptors and to be reduced time-dependently by desensitization with either iO-4 M histamine or 10' M carbachol. 2 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. 3 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 H,-receptors. 4 After desensitization with carbachol, but not histamine, the contractile response to 5 x 1O 2M caffeine in Ca-free solution was significantly reduced. 5 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 Hl-receptors.

Different profiles of desensitization dynamics in guinea‐pig jejunal longitudinal smooth muscle after stimulation with histamine and methacholine

“…It has been shown that histamine responses can be modulated in vivo (Manning et al, 1987) and in vitro. Histamine-induced desensitization of the H1-receptor has been documented in various isolated cell systems (Lewis Baenzinger et al, 1981;Brown et al, 1986;Nakahata & Harden, 1987;McDonough et al, 1988) and smooth muscle preparations (Anderson et al, 1979;Kenakin & Cook, 1979;Bielkiewicz & Cook, 1984;Hishinuma & Uchida, 1988).…”

Blockade by the local anaesthetic, tetracaine, of desensitization of Ca‐induced Ca release after muscarinic stimulation in smooth muscle

“…That is, the K+-induced contraction was more rapid and the tonic tension was not maintained after treatment with carbachol as shown in Figure 1. On the other hand, there was no change in the K+-induced contractions in the histamine-induced desensitized state as shown in Figure 2 and in our previous paper (Hishinuma & Uchida, 1988 (a(i)). (b) (ii) Conditions were as in (a(ii)) except that 3 x 10-5M dibucaine was used instead of tetracaine.…”

“…We have been investigating muscarinic and histamine desensitization of smooth muscle contraction. We have found that contractions dependent on the release of intracellularly stored Ca elicited by carbachol, histamine and caffeine were heterologously desensitized by carbachol, while histamine homologously desensitized the histamine-elicited contraction (Hishinuma & Uchida, 1988). We concluded that desensitization induced by carbachol and histamine was due to the functional changes of intracellular Ca stores and histamine H,-receptors, respectively.…”

“…After the desensitizing treatment with carbachol in the absence of local anaesthetics (desensitization), contractile responses in Ca-free solution elicited by carbachol, histamine and caffeine were reduced to about 60%, 40%, and 60% of the control, respectively. This heterologous desensitization induced by carbachol was thought to occur due to changes in the intracellular Ca stores (Hishinuma & Uchida, 1988). When high concentrations of local anaesthetics were used, they remained in the muscles even after washing, and reduced K+-induced contractions probably due to their inhibitory effects on voltage-dependent Ca channels (Spedding & Berg, 1985).…”

“…There was no significant reduction in the carbachol-, histamine-and caffeine-elicited contractions after treatment with local anaesthetics alone (drug alone), except in the case of carbachol-elicited contraction after treatment with 3 x 10-s M dibucaine and histamine-elicited contractions after treatment with tetracaine and dibucaine. Desensitization in the absence of local anaesthetics (desensitization) was compared with that in the presence of the local anaesthetics (Hishinuma & Uchida, 1988). That is, the K+-induced contraction was more rapid and the tonic tension was not maintained after treatment with carbachol as shown in Figure 1.…”