Abstract
1 Short-term desensitization to histamine was induced by incubating guinea-pig taenia caecum with 10(-4)M histamine for 30 min (desensitizing incubation) in normal Locke-Ringer solution or Ca-free Locke-Ringer solution containing 0.2 mM EGTA. This desensitization was measured as a reduction of the maximal contractile response. 2 The effects of the presence of local anaesthetics during the desensitizing incubation were examined. Results showed that tetracaine, procaine, procainamide, oxybuprocaine and lignocaine inhibited the desensitization, whereas dibucaine, benzocaine and mepivacaine did not. 3 The inhibitory effects of these drugs on the desensitization were not correlated with their lipid solubility nor with the potency of their known effects, such as membrane stabilization, Ca channel blockade, calmodulin antagonism, or inhibition of C-kinase. 4 It is concluded that the inhibitory effects of local anaesthetics on the desensitization are not due to their non-specific membrane-stabilizing effects per se, but to some other action.
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Selected References
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- Barsoum G. S., Gaddum J. H. The pharmacological estimation of adenosine and histamine in blood. J Physiol. 1935 Aug 22;85(1):1–14. doi: 10.1113/jphysiol.1935.sp003298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bielkiewicz B., Cook D. A. The mechanism of the histamine-induced desensitization of guinea-pig ileum. Gen Pharmacol. 1984;15(1):51–54. doi: 10.1016/0306-3623(84)90080-6. [DOI] [PubMed] [Google Scholar]
- Heidmann T., Changeux J. P. Structural and functional properties of the acetylcholine receptor protein in its purified and membrane-bound states. Annu Rev Biochem. 1978;47:317–357. doi: 10.1146/annurev.bi.47.070178.001533. [DOI] [PubMed] [Google Scholar]
- Higuchi H., Uchida S., Matsumoto K., Yoshida H. Inhibition of agonist-induced degradation of muscarinic cholinergic receptor by quinacrine and tetracaine--possible involvement of phospholipase A2 in receptor degradation. Eur J Pharmacol. 1983 Oct 28;94(3-4):229–239. doi: 10.1016/0014-2999(83)90412-0. [DOI] [PubMed] [Google Scholar]
- Kenakin T. P., Cook D. A. The effect of desensitization on the antagonism of the histamine response by phenoxybenzamine. Mol Pharmacol. 1980 May;17(3):309–313. [PubMed] [Google Scholar]
- Kunze H., Bohn E., Vogt W. Effects of local anaesthetics on prostaglandin biosynthesis in vitro. Biochim Biophys Acta. 1974 Sep 19;360(3):260–269. doi: 10.1016/0005-2760(74)90055-1. [DOI] [PubMed] [Google Scholar]
- Magaribuchi T., Ito Y., Kuriyama H. Desensitization of smooth muscle cells in the guinea pig taenia coli to prolonged application of carbachol. Jpn J Physiol. 1973 Oct;23(5):447–464. doi: 10.2170/jjphysiol.23.447. [DOI] [PubMed] [Google Scholar]
- Mori T., Takai Y., Minakuchi R., Yu B., Nishizuka Y. Inhibitory action of chlorpromazine, dibucaine, and other phospholipid-interacting drugs on calcium-activated, phospholipid-dependent protein kinase. J Biol Chem. 1980 Sep 25;255(18):8378–8380. [PubMed] [Google Scholar]
- Quach T. T., Duchemin A. M., Rose C., Schwartz J. C. Specific desensitization of histamine H1 receptor-mediated [3H]glycogen hydrolysis in brain slices. Mol Pharmacol. 1981 Sep;20(2):331–338. [PubMed] [Google Scholar]
- Spedding M., Berg C. Antagonism of Ca2+-induced contractions of K+-depolarized smooth muscle by local anaesthetics. Eur J Pharmacol. 1985 Jan 22;108(2):143–150. doi: 10.1016/0014-2999(85)90718-6. [DOI] [PubMed] [Google Scholar]
- Stadel J. M., Nambi P., Shorr R. G., Sawyer D. F., Caron M. G., Lefkowitz R. J. Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3173–3177. doi: 10.1073/pnas.80.11.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor J. E., Richelson E. Desensitization of histamine H1 receptor-mediated cyclic GMP formation in mouse neuroblastoma cells. Mol Pharmacol. 1979 May;15(3):462–471. [PubMed] [Google Scholar]
- Uchida M. K., Mita M. Effects of Quin-2, an intracellular Ca chelator, and TMB-8, an intracellular Ca antagonist, on the short-term desensitization to histamine in guinea pig taenia caecum. Gen Pharmacol. 1985;16(5):449–453. doi: 10.1016/0306-3623(85)90003-5. [DOI] [PubMed] [Google Scholar]
- Uchida M., Hirano H. Desensitization to histamine in the absence of external Ca++ in the guinea-pig taenia caecum. Experientia. 1983 Aug 15;39(8):862–863. doi: 10.1007/BF01990406. [DOI] [PubMed] [Google Scholar]
- Volpi M., Sha'afi R. I., Epstein P. M., Andrenyak D. M., Feinstein M. B. Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin. Proc Natl Acad Sci U S A. 1981 Feb;78(2):795–799. doi: 10.1073/pnas.78.2.795. [DOI] [PMC free article] [PubMed] [Google Scholar]