The Compartmentalized Hypothalamo-Neurohypophysial System: Evidence for a NeurohypophysialAction of Acetylcholine on Vasopressin Release

Abstract

A portion of medial basal hypothalamus containing the supraoptic nuclei with the neurohypophysis attached was organ cultured. Hypothalamus and neurohypophysis were maintained in separate compartments, and the intact infundibular stalk passed through a hole in a fluid-tight barrier which separated the two compartments. After 24, 48 and 72 h in culture, vasopressin (VP) release from the neurohypophysis was measured during a control hour and again during an immediately subsequent test hour. Test hour VP release was expressed as a percentage of control hour release. Test substances were added to either the pituitary or the hypothalamus compartment. Acetylcholine stimulated pituitary VP release both when added to hypothalamus (10^–5M) and when added directly to neural lobe (10^–6 M and above). Acetylcholine 10^–5 M and no effect when isolated neural lobes (severed from hypothalamus to culture) were similarly tested. Hexamethonium blocked the stimulation of pituitary VP release evoked by addition of acetylcholine to hypothalamus. However, in pituitary, atropine prevented the stimulatory effect of acetylcholine. Atropine had no effect on VP release from severed neural lobes. These data show that high concentrations of acetylcholine can stimulate VP release from pituitary both by a hypothalamic action and also by a direct effect in neural lobe. Further, a nicotinic cholinergic receptor mediates the action of acetylcholine in hypothalamus whereas a muscarinic cholinergic receptor is involved in the direct pituitary response to acetylcholine. Intact axonal connections between hypothalamus and pituitary are required in order for acetylcholine to stimulate VP release in neurohypophysis.

Pituitary-Adrenal Cortical Responses to Low-Dose Physostigmine and Arginine Vasopressin Administration in Normal Women and Men

“…There also were no significant female-male differences in ACTH or cortisol responses to AVP. In contrast, the men had significantly greater ACTH There is ample evidence from animal studies that cholinergic neurotransmission stimulates both CRH and arginine vasopressin (AVP) secretion (Gregg 1985;Tuomisto and Männistö 1985;Assenmacher et al 1987;Tsagarakis and Grossman 1990;Michels et al 1991;Okuda et al 1993;Whitnall 1993;Coiro et al 1995;Calogero 1995;Ohmori et al 1995), both of which stimulate ACTH secretion (Rivier et al 1990;Antoni 1993). Several studies in humans, however, suggest that the hypothalamo-pituitary-adrenal cortical (HPA) axis is activated only by doses of cholinergic agonists that produce noxious side effects, especially nausea (Carroll et al 1980;Davis et al 1982;Doerr and Berger 1983;Nurnberger et al 1983;Lewis et al 1984;Krieg et al 1987;Freeman et al 1990), and, by inference, a nonspecific stress response, nausea being a powerful stimulus to AVP release (Nussey et al 1988;Koch et al 1990;Kohl 1992).…”

“…There also were no significant female-male differences in ACTH or cortisol responses to AVP. In contrast, the men had significantly greater ACTH There is ample evidence from animal studies that cholinergic neurotransmission stimulates both CRH and arginine vasopressin (AVP) secretion (Gregg 1985;Tuomisto and Männistö 1985;Assenmacher et al 1987 Received March 20, 1998; revised July 1, 1998; accepted July 10, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL .…”

Nicotinic acetylcholine receptors in porcine hypophyseal intermediate lobe cells.

“…Indeed activation of central-type nicotinic receptors (sensitive to toxin F antagonism) does cause a strong stimulation of dopamine release in the striatum (Giorguieff, Le Floc'h, Westfall, Glowinski & Besson, 1977;Schultz & Zigmond, 1989). On the other hand muscarinic inhibition of hypothalamo-hypophyseal pathways will stimulate pituitary function (Gregg, 1985). Such a phenomenon may in part explain the somewhat slow but sustained excitatory effect of ACh first described in rats by Hadley, Hruby & Bower (1975) and more recently in the frog IL by Louiset et al (1989).…”

“…Only autoradiographic studies on the intact gland combined with binding studies on isolated cells can fully resolve this problem. The only evidence to date for pituitary muscarinic receptors is that of quisnuclididinyl-benzilate binding sites in the neurointermediate lobe of the rat (Tolliver, Taylor & Burt, 1981;Gregg, 1985) and pirenzepine-sensitive secretory responses to ACh in the frog (Louiset et al 1989). To our knowledge there are no conclusive reports of ligand binding studies aimed at detecting either nicotinic or muscarinic receptors on either freshly dispersed or cultured cells.…”

Sexual Diergism of Hypothalamo-Pituitary–Adrenal Cortical Responses to Low-Dose Physotigmine in Elderly vs. Young Women and Men

“…Cholinergic neurotransmission stimulates both corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) secretion (Gregg 1985;Tuomisto and Männistö 1985;Assenmacher et al 1987;Tsagarakis and Grossman 1990;Michels et al 1991;Okuda et al 1993;Whitnall 1993;Coiro et al 1995;Calogero 1995;Ohmori et al 1995;Pascualy et al 1995), both of which stimulate adrenocorticotropic hormone (ACTH) secretion (Rivier et al 1990;Antoni 1993). Because cholinergic agonists produce noxious side effects, especially nausea, and by inference a nonspecific stress response, we established a dose of physostigmine (PHYSO), a reversible cholinesterase inhibitor, that discernibly elevated plasma ACTH and cortisol concentrations in normal young adult subjects but produced few or no side effects (Rubin et al 1999a).…”