Summary
In an experimental model of bleeding-induced hemorrhagic shock causing the death of all saline-treated rats within 30 min, the intravenous injection of ACTH-(1–24) at the dose of 160 μg/kg induced a sustained reversal of the shock condition, with almost complete recovery of blood pressure, pulse amplitude, respiratory rate, heart rate, and 100% survival, at least for the 2 h of observation. This effect of ACTH-(1–24) was prevented by the intracerebroventricular injection of 4-DAMP (a highly selective antagonist for M1 and M3 muscarinic receptors), but unaffected by the intracerebroventricular injection of pirenzepine (a highly selective antagonist for M1 muscarinic receptors). These data indicate that an essential step in the complex mechanism of the ACTH-induced shock reversal may be the activation of brain M3 muscarinic receptors.
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References
Barlow RB, Shepherd MK (1985) A search for selective antagonists at M2 muscarinic receptors. Br J Pharmacol 85:427–435
Bertolini A, Guarini S, Ferrari W (1986a) Adrenal-independent, anti-shock effect of ACTH-(1–24) in rats. Eur J Pharmacol 122:387–388
Bertolini A, Guarini S, Ferrari W, Rompianesi E (1986b) Adrenocorticotropin reversal of experimental hemorrhagic shock is antagonized by morphine. Life Sci 39:1271–1280
Bertolini A, Guarini S, Rompianesi E, Ferrari W (1986c) α-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock. Eur J Pharmacol 130:19–26
Bertolini A, Guarini S, Ferrari W, Noera G, Massini C, Di Tizio S (1987) ACTH-(1–24) restores blood pressure in acute hypovolaemia and haemorrhagic shock in humans. Eur J Clin Pharmacol 32:537–538
Birdsall NJM, Hulme EC (1983) Muscarinic receptor subclasses. Trends Pharmacol Sci 4:459–463
Brezenoff HE, Giuliano R (1982) Cardiovascular control by cholinergic mechanisms in the central nervous system. Annu Rev Pharmacol Toxicol 22:341–381
Burgen ASV (1984) Muscarinic receptor — an overview. Trends Pharmacol Sci 5 [Suppl]:1–3
Caulfield MP, Higgins GA, Straughan DW (1983) Central administration of the muscarinic receptor subtype-selective antagonist pirenzepine selectively impairs passive avoidance learning in the mouse. J Pharm Pharmacol 35:131–132
Ciriello J, Caverson MM, Polosa C (1986) Function of the ventrolateral medulla in the control of the circulation. Brain Res Rev 11:359–391
Collins JA, Braitberg A, Margraf HW, Butcher HR (1969) Hemorrhagic shock in rats. Arch Surg 99:484–488
Delmendo RE, Michel AD, Whiting RL (1989) Affinity of muscarinic receptor antagonists for three putative muscarinic receptor binding sites. Br J Pharmacol 96:457–464
Doods HN, Mathy M-J, Davidesko D, Van Charldorp KJ, De Jonge A, Van Zwieten PA (1987) Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2, and M3 receptors. J Pharmacol Exp Ther 242:257–262
Eglen RM, Whiting RL (1986) Muscarinic receptor subtypes: a critique of the current classification and a proposal for a working nomenclature. J Auton Pharmacol 5:323–346
Ellis J, Hoss W (1980) Analysis of regional variations in the affinities of muscarinic agonists in the rat brain. Brain Res 193:189–198
Giachetti A, Micheletti R, Montagna E (1986) Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist. Life Sci 38:1663–1672
Giuliano R, Ernsberger P, Arango V, Ruggiero D, Reis DJ (1986) Cholinergic mechanisms in rostral ventrolateral medulla (RVL) participate in the tonic control of arterial pressure (AP) and mediate vasopressor action of systemically administered physostigmine. Soc Neurosci Abstr 12:964
Giuliano R, Ruggiero DA, Morrison S, Ernsberger P, Reis DJ (1989) Cholinergic regulation of arterial pressure by the C1 area of the rostral ventrolateral medulla. J Neurosci 9:923–942
Guarini S, Rompianesi E, Ferrari W, Bertolini A (1986) Influence of vagotomy and of atropine on the anti-shock effect of adrenocorticotropin. Neuropeptides 8:19–24
Guarini S, Ferrari W, Bertolini A (1988) Involvement of the sympathetic nervous system in the cardiovascular effects of ACTH-(1–24) during hemorrhagic shock in rats. Naunyn-Schmiedeberg's Arch Pharmacol 337:556–560
Guarini S, Tagliavini S, Bazzani C, Ferrari W, Bertolini A (1989) The endogenous antagonists of opioid peptides in the management of hemorrhagic shock. J Endocrinol Invest 12:145–147
Guarini S, Tagliavini S, Bazzani C, Ferrante F, Bertolini A (1990) Intracerebroventricular injection of hemicholinium-3 prevents the ACTH-induced, but not the physostigmine-induced, reversal of hemorrhagic shock in rats. Pharmacology 40:85–89
Guertzenstein PG (1973) Blood pressure effects obtained by drugs applied to the ventral surface of the brain stem. J Physiol (Lond) 229:395–408
Hammer R, Giachetti A (1982) Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization. Life Sci 31:2991–2998
Hammer R, Giraldo E, Schiavi GB, Monferini E, Ladinsky H (1986) Binding profile of a novel cardioselective muscarine receptor antagonist, AF-DX 116, to membranes of peripheral tissues and brain in the rat. Life Sci 38:1653–1662
Mitchelson F (1984) Heterogeneity in muscarinic receptors: evidence from pharmacologic studies with antagonists. In: Proceedings of the international symposium on subtypes of muscarinic receptors. Trends Pharmacol Sci [Suppl]:12–16
Mutschler E, Moser U, Wess J, Lambrecht G (1988) New approaches to the subclassification of muscarinic receptors. In: Melchiorre C, Gianella M (eds) Recent advances in receptor chemistry, vol 11. Elsevier, Amsterdam New York, pp 195–217
Noera G, Pensa P, Guelfi P, Biagi B, Curcio C, Bentini C (1989) ACTH-(1–24) and hemorrhagic shock: preliminary clinical results. Resuscitation 18:145–147
Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxis atlas of the rat brain. Plenum, New York
Pinelli G, Chesi G, Di Donato C, Reverzani A, Marani L (1989) Preliminary data on the use of ACTH-(1–24) in human shock condition. Resuscitation 18:149–150
Reis DJ, Ross CA, Granata AR, Ruggiero DA (1987) Role of C1 area of rostroventrolateral medulla in cardiovascular control. In: Buckley JP, Ferrario CM (eds) Brain peptides and catechol amines in cardiovascular regulation. Raven, New York, pp 1–14
Reis DJ, Ruggiero DA, Morrison SF (1989) The C1 area of rostral ventrolateral medulla: a central site integrating autonomic responses to hemorrhage. Resuscitation 18:269–288
Varagić V (1955) The action of eserine on the blood pressure of the rat. Br J Pharmacol Chemother 10:349–353
Willette RN, Barcas PP, Krieger AJ, Sapru HN (1983) Vasopressor and depressor areas in the rat medulla. Identification by microinjection of L-glutamate. Neuropharmacology 22:1071–1079
Willette RN, Punnen S, Krieger AJ, Sapru HN (1984) Cardiovascular control by cholinergic mechanisms in the rostral ventrolateral medulla. J Pharmacol Exp Ther 231:457–463
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Guarini, S., Tagliavini, S., Bazzani, C. et al. Brain M3 muscarinic receptors are involved in the ACTH-induced reversal of hemorrhagic shock. Naunyn-Schmiedeberg's Arch Pharmacol 342, 36–39 (1990). https://doi.org/10.1007/BF00178969
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DOI: https://doi.org/10.1007/BF00178969