Temperature‐dependence of desensitization induced by acetylcholine and histamine in guinea‐pig ileal longitudinal muscle

Abstract

1The effects of temperature on the time course of desensitization induced by acetylcholine and histamine, and on the recovery from desensitization were studied in the longitudinal muscle of the guinea-pig ileum.2 Self-and cross-desensitization produced by acetylcholine (10-M) occurred rapidly in the first 1Omin of exposure to the agonist, with the same time course and the same degree of desensitization over the temperature range of 1 C to 31°C. 3 Self-desensitization produced by histamine (10 5M) also occurred rapidly in the first 10min of exposure to the agonist, and showed great temperature-dependence, especially at 1 C and 21°C, but scarcely occurred at 6°C. 4 Cross-desensitization produced by histamine developed gradually with time and showed a moderate temperature-dependence between 1 C and 31°C, but scarcely occurred at 6°C. 5 The recovery processes from desensitization showed marked temperature-dependence. Recovery was halted completely at 1 1C. 6 These studies suggest that acetylcholine-induced desensitization may be attributed to a single nonspecific mechanism. Histamine-induced desensitization may be due to at least two mechanisms: it occurs in both a specific and non-specific manner. Each of these desensitizations can be characterized by its unique temperature-dependence.

Alterations in histamine receptors of guinea‐pig ileal smooth muscle produced during agonist‐induced desensitization

“…It has been proposed that histamine-induced desensitization of guinea-pig ileal smooth muscle occurs at the receptor level (Kenakin & Cook, 1980;Bielkwiewicz & Cook, 1984), and our previous study (Horio et al, 1990) supported this view. The aim of the present study was, then, to determine if agonist treatments which led to desensitization of the histamine response were accompanied by alterations in histamine receptors.…”

“…It is possible that such receptors are functionally impaired in their coupling to the effector component leading to a decreased response to the agonist, that is, desensitization. The time course of the affinity change of the receptor (see Figure 3) was similar to that of histamineinduced desensitization which was observed previously (Horio et al, 1990), further supporting the view that the alteration in histamine receptors is the cause of desensitization.…”

“…These authors suggested that histamine-induced desensitization involved changes at the receptor level. Our previous study (Horio et al, 1990) confirmed this proposition. At present, however, there is no direct evidence which indicates the involvement of the receptor molecule in the histamineinduced desensitization processes.…”

“…We previously demonstrated (Horio et al, 1990) that a 30-min exposure to I0-`-I-I M histamine caused substantial desensitization of guinea-pig ileal smooth muscle. In the present study, we examined whether such agonist treatment which led to desensitization of the histamine response also caused alter- Hill & Young (1981).…”

Characteristics of the binding of [3H]‐mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine‐induced H1‐receptor internalisation

“…Hunyady et 1991), brain slices (Quach et al, 1981;, acetylcholine (Koenig & Edwardson, 1994, and recells in culture (Taylor & Richelson, 1979;Brown et al, 1986; ferences therein) and noradrenaline (Leeb-Lunberg et al, 1987;Nakahata & Harden, 1987;Dillon-Carter & Chuang, 1989;Hausdorff et al, 1990). However, although there have been Cowlen et al, 1990;Smit et al, 1992;Bristow & 7amani, 1993; numerous studies of the mechanisms involved in the desensi- Dickenson & Hill, 1993;McCreath et al, 1994), a number of tization of responses to histamine at Hi-receptors in intestinal which have provided evidence for changes at the level of the smooth muscle (Barsoum & Gaddum, 1935;Cantoni & Eastreceptor (Brown et al, 1986;Nakahata & Harden, 1987;Hishinuma & Uchida, 1988;Cowlen et al, 1990;Horio et al, 1990b; Leurs et al, 1990;Dickenson & Hill, 1993) which will cross the cell membrane and bind to intracellular IkkW Joumal of Pharmacoloa (1995) 116, 2715-2723 sites and become concentrated in compartments with a low pH, have been noted some years ago (Maloteaux et al, 1983). We have attempted to avoid these difficulties by synthesizing a quaternary amine radioligand for the H1-receptor, [3H]-(+)-N-methyl-4-methyldiphenhydramine ([3H]-QMDP), which should bind only to sites on the plasma membrane (Treherne & Young, 1988a (Wallace & Young, 1983;Treherne & Young, 1988b), which should allow extensive washing of cells, and (b) the availability of non-penetrant and penetrant HI-receptor antagonists, which might be used to determine binding to plasma membrane HI-receptors and plasma membrane+ intracellularreceptors, respectively.…”