Interaction of Vasopressins and Linear N‐Terminal ACTH Fragments in the Induction of Natriuresis

Cort, J. H.; Nováková, J.; Škopková, Jana

doi:10.1111/j.1365-2362.1974.tb00406.x

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…In addition, we now find ,e than 15 in that synthetic Ala-Gly-[Arge]-vasopresago as 1966 sin mimics the chromatographic behavresidues at-ior and physiological activity of the natue added res-ral product with the same sequence. opeptidases Second, our observations do not conor Gly, but tradict in any way evidence supporting a -rs) they are hypothalamic site or sites for vasopressee (5)] just sin synthesis although our observations [ow this re-will necessarily alter our view of the lone,'" how-chemical forms in which arginine vasopressin is transported. Third, the idea J. H. CORT that prohormone sequences are invariant id seems unwarranted, since there are clear lical precedents for variability in an individual or members of a species that could explain our observations.…”

contrasting

confidence: 54%

Arginine vasopressin in extracts of bovine pituitary

Cort¹

1980

Science

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contrasting

confidence: 54%

Arginine vasopressin in extracts of bovine pituitary

Cort¹

1980

Science

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“…However, the role of other ACTH fragments in the regulation of food intake and body weight is not clear. More emphasis has been given to the effect of these fragments on insulin secretion [12], cardiovascular [13], renal [14], human mental performance [15] and imprinting behaviour [16] and other CNS indications [17].…”

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confidence: 99%

C-Terminal Fragments of ACTH Stimulate Feeding in Fasted Rats

Al-Barazanji¹,

Miller²,

Rice³

et al. 2001

Horm Metab Res

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Peptides derived from pro-opiomelanocortin, including alpha-MSH and ACTH, play important roles in the regulation of feeding. We investigated the central effect of ACTH 1-39 (ACTH) and peptides derived from the N-terminus (ACTH 1-10, Acetyl-ACTH 1-13-amide [alpha-MSH]) and C-terminus (ACTH 18-39 and ACTH 22-39) of this peptide on feeding in 16 hour-fasted or rats fed ad libitum. As expected, ACTH reduced feeding in fed and previously fasted rats, although this anorectic effect was more pronounced in fasted rats. The N-terminal-derived peptide alpha-MSH, but not ACTH 1-10, reduced cumulative food intake over 2 h after its injection intracerebroventricularly (icv) in 16 h-fasted, but not in fed rats. In contrast, the C-terminal fragments produced a long-lasting increase in feeding in fasted, but not in fed rats. The anorectic effects of N-terminal fragments of ACTH are recognised to be mediated via melanocortin MC4 receptors. However, the orexigenic effects of the C-terminal fragments do not appear to be conducted via MC4 receptors, since neither ACTH 18-39 nor ACTH 22-39 stimulated cAMP accumulation nor inhibited the ACTH-stimulated cAMP accumulation in HEK-293 cells transfected with the recombinant MC4 receptor.

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“…There are, however, wide variations in different response sensitivities. Thus, for example, single 10-13mol/kg doses are antidiuretic in most species, IO-llmol/kg doses begin to be pressor (10,38) and mol/kg doses begin to be natriuretic (10,13). Quite naturally, the higher the sensitivity of the response, the greater the physiological importance 'Address: Institute of Physiology, Academy of Sciences, Prague.…”

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Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

Cort

Albrecht

Nováková

et al. 1975

Eur J Clin Investigation

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Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbC1. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the followin8 of its analogues: a) with extended peptide chains at the N-terminal (including "hormonogens") N -glycyl-glycyl-glycyl-lysine-vasopressin, Na-glycyl-glycyl-glycyl-arginine-vasopressin and N -D-va lyl-1 y s ine-vas o pr e s s in, b) I' carba" mod if i ca t ions de s amino-c ar baar g in ine-vas o p r e s s in, desamho-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarbaarginine-vasopressin and c) other steric alterationsdesamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 6 0 min. The presence of steric alterations in the C-terminal tripeptide of the molecule-D-arginine or N-methylarginine in sequence position 8practically completely eliminated vascular activity. The same was true for N -D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-s-, -SCH2 and -CHzCH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and congtihte the limiting factor determining complex duration, or persistence of the active peptide in the "receptor compartment". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and utezus and for induction of menstruation.

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Interaction of Vasopressins and Linear N‐Terminal ACTH Fragments in the Induction of Natriuresis

Cited by 7 publications

References 13 publications

Arginine vasopressin in extracts of bovine pituitary

Arginine vasopressin in extracts of bovine pituitary

C-Terminal Fragments of ACTH Stimulate Feeding in Fasted Rats

Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity

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