His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and alpha-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 micrograms i.v.) increased basal GH levels from 2.6 +/- 1.5 to 14.4 +/- 3.1 micrograms/l (mean +/- S.E.M.) after 15 min. GHRH (50 micrograms i.v.) induced a GH peak of 9.7 +/- 2.2 micrograms/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 +/- 9.0 micrograms/l (P < 0.01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37.9 +/- 10.1 micrograms/l P < 0.05), while the muscarinic blocker atropine (100 micrograms i.v.) completely abolished (GH peak lower than 2 micrograms/l) the stimulatory action of GHRP-6. On the other hand, administration of the alpha-2 adrenergic agonist clonidine (4 micrograms/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6.(ABSTRACT TRUNCATED AT 250 WORDS)