Responses of Plasma Oxytocin and Arginine Vasopressin to Nausea Induced by Apomorphine and Ipecacuanha

Abstract

Apomorphine, a centrally-acting emetic, was administered subcutaneously (50 micrograms/kg) to nine normal subjects (four male, five female; aged 22-36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24-49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9.5 +/- 0.9 min which was followed by a large increase in plasma arginine vasopressin (AVP) concentration (from 0.9 +/- 0.2 pmol/l to 249 +/- 104 pmol/l at 15 min after the onset of symptoms; mean +/- SEM, P less than 0.01). There was a small but significant increase in plasma oxytocin (OXT) concentration (from 1.6 +/- 0.4 pmol/l to 6.2 +/- 3.4 pmol/l; P less than 0.05). Mean arterial pressure (MAP) fell slightly (from 87 +/- 1.9 mm Hg to 71 +/- 4.4 mm Hg; P less than 0.05) 15 min after the onset of nausea; there was no change in blood haematocrit or plasma osmolality and sodium concentration. In the DI patients apomorphine produced nausea (with vomiting in three of four) with a latency of 10.0 +/- 1.4 min but failed to cause an increase in either plasma AVP or OXT. In the DI patients the fall in MAP did not reach statistical significance (83 +/- 4 mm Hg to 71 +/- 11 mm Hg); there was also no change in haematocrit, osmolality or sodium concentration. Ipecacuanha, an emetic with both peripheral and central actions, was administered orally to seven normal subjects (three male, four female; aged 22-36 years) six of whom also underwent apomorphine tests.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…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). In the present study, a dose of physostigmine (PHYSO), a reversible cholinesterase inhibitor, was established that discernibly elevated plasma ACTH and cortisol concentrations in normal subjects but produced few or no side effects.…”

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

“…Administration of vasopressin at supraphysiological doses produced nausea in humans, but when vasopressin was infused to match the plasma level during nausea induced by motion nausea was not reported (Kim et al, 1997). Additionally, apomorphine induces nausea in patients with idiopathic diabetes insipidus despite the absence of an increase in plasma vasopressin (Nussey et al, 1988). Although this does not exclude a role for vasopressin in the genesis of nausea in intact individuals, it is a clear that a rise in plasma vasopressin is not essential for the production of nausea under all circumstances and taken together with the studies of vasopressin infusion and plasma levels could indicate that vasopressin requires an additional factor(s) to be present for the induction of nausea when it is released at a lower concentration.…”

“…Studies in rat show elevated plasma cortisol levels with the production of CFA (Smotherman, 1985). Additionally (as mentioned above), there are many potential candidate hormones that might contribute to nausea, including vasopressin, oxytocin, adrenaline, growth hormone, prolactin, adrenocorticotrophic hormone, and pancreatic polypeptide (Eversmann et al, 1978;Feldman et al, 1988;Nussey et al, 1988;Page et al, 1990;Xu et al, 1993). However, the challenge with all the systemic signals for nausea is to understand where and how they gain access to the central nervous system (e.g.…”

“…Despite a focus on vasopressin secretion as a correlate of nausea (and oxytocin as a correlate of malaise in the rat) other hormones are increased in subjects with nausea induced by apomorphine, ipecac, and motion, including adrenaline, cortisol, growth hormone, prolactin, adrenocorticotrophic hormone, and pancreatic polypeptide (Eversmann et al, 1978;Feldman et al, 1988;Nussey et al, 1988;Page et al, 1990;Xu et al, 1993). It remains to be determined whether any of these hormones are related to the genesis for the sensation of nausea in contrast to being indicators of the generally "stressful" nature of malaise.…”

Arginine vasopressin – a mediator of chemotherapy induced emesis?

“…On the other hand, we know that nausea and vomiting occur in patients with diabetes insipidus treated with apomorphine in the absence of any change in AVP levels (Nussey et al, 1988). In addition, patients treated with ipecacuahna did not exhibit changes in AVP levels despite symptoms of nausea and emesis similar to that following apomorphine, where large increases in AVP were observed (Nussey et al, 1988). However, it should be remembered that for such a sophisticated reflex it is likely that there are many pathways involved.…”