title: Hormonal effects of apomorphine and cholecystokinin in pigs: modification of the response to cholecystokinin by a dopamine antagonist (metoclopramide) and a kappa opioid agonist (PD117302).
abstract: Three experiments were carried out to investigate some of the mechanisms involved in the endocrine responses of pigs to the emetic agents apomorphine and cholecystokinin. In Experiment 1, plasma levels of vasopressin and cortisol were measured in prepubertal pigs (N = 5) treated with i.v. apomorphine (25 micrograms/kg) or saline vehicle. In Experiment 2, concentrations of vasopressin and cortisol were determined in pigs given iv sulphated cholecystokinin octapeptide (1.3 micrograms/kg), metoclopramide (300 micrograms/kg), metoclopramide + cholecystokinin, and an oral dose of the kappa opioid agonist PD 117302 (20 micrograms) alone, or followed by i.v. cholecystokinin. In Experiment 3, operant feeding behaviour was quantified in pigs (N = 4) given cholecystokinin (1 microgram/kg) or cholecystokinin preceded by oral PD 117302. Following apomorphine injection in Experiment 1, there was a rapid, transient, rise in plasma vasopressin. Cholecystokinin had a similar effect on vasopressin secretion in Experiment 2 and also induced a later rise in plasma cortisol. Pre-treatment with metoclopramide appeared to reduce both of these effects of cholecystokinin, but only the decrease in cortisol was statistically significant. However, oral administration of PD 117302 abolished the effect of cholecystokinin on vasopressin release and reduced the subsequent rise in cortisol. The inhibitory effect of cholecystokinin on feeding was unaltered by PD 117302 treatment in Experiment 3. The results obtained with apomorphine and metoclopramide, together, suggest that the neuroendocrine effects of cholecystokinin in the pig may involve an action on central dopamine receptors while the effects of PD 117302 indicate that kappa opioids may modify the hormonal responses to cholecystokinin by a peripheral action.
authors.affiliation: AFRC Institute of Animal Physiology and Genetics Research, Cambridge Research Station, UK.
authors.forename: R F
authors.initials: RF
authors.lastname: Parrott
authors.forename: I S
authors.initials: IS
authors.lastname: Ebenezer
authors.forename: B A
authors.initials: BA
authors.lastname: Baldwin
authors.forename: M L
authors.initials: ML
authors.lastname: Forsling
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism*; D008236:Lypressin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D013552:Swine; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D011758:Pyrroles; D013876:Thiophenes; C054718:PD 117302; D008236:Lypressin; D002766:Cholecystokinin; D008787:Metoclopramide; D001058:Apomorphine; D006854:Hydrocortisone