Conversion and Inactivation of Neuropeptides

Marks, Neville

doi:10.1007/978-1-4613-4130-7_9

Cited by 40 publications

(15 citation statements)

References 165 publications

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“…In this respect, our rCBF values do not represent the maximum changes in blood flow that can be evoked with VIP at the 10jiig/ml concentration. Finally, there are multiple peptidases and peptide reuptake mechanisms which are active on other peptides in the central nervous system (Marks, 1977). The effect of these enzymes on VIP is unknown.…”

Section: The Effect Of Intraventricular Vipmentioning

confidence: 99%

Vasoactive intestinal polypeptide and the canine cerebral circulation.

Wilson¹,

O'Neill²,

Said³

et al. 1981

Circulation Research

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A potential role for cerebrovascular nerves containing vasoactive intestinal polypeptide (VIP) was examined in 24 anesthetized, ventilated dogs. Cerebral blood flow (CBF) was measured by either the cerebral venous outflow or microsphere method. Plasma VIP concentration was measured by radioimmunoassay. Hypercapnia (5% and 10% CO2) and hypoxia (7% O2) produced significant increases in cerebral venous outflow, but had no affect on arterial or cerebral venous VIP concentrations. Measurements of VIP in cerebrospinal fluid (CSF) made during 5% and 8% CO2 breathing also were not different from control values. VIP produced large dose-dependent increases in common carotid artery and temporalis muscle blood flow when injected or infused intraarterially; however, VIP had no effect on total or regional cerebral blood flow (rCBF) within the brain when administered in a similar manner. Unilateral perfusion of the cerebral ventricles with VIP produced significant increases (range: 11-80%) in rCBF. These data are consistent with the possibility that local release of VIP from perivascular nerve endings could affect CBF. The unresponsiveness of canine cerebral vessels to blood-borne VIP may be due to the blood-brain barrier, since VIP dilates cerebral vessels when the barrier is bypassed by intraventricular infusion. These studies do not support the hypothesis that CBF changes induced during hypercapnia or hypoxia are mediated by VIP.

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Section: The Effect Of Intraventricular Vipmentioning

confidence: 99%

Vasoactive intestinal polypeptide and the canine cerebral circulation.

Wilson¹,

O'Neill²,

Said³

et al. 1981

Circulation Research

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“…Arylamidases are among such enzymes, the activities of which can be measured by analysing the hydrolysis of artificial substrates like aminoacyl-ß-naphthylamides (aa-ß-NA; arylamides). Although arylamidases have been implicated in the degradation of several neuropeptides (2), their functional role in the brain is still unknown. The possible endogen¬ ous substrates could be neuropeptides containing the same amino acid at the N-terminal position as arylamides, in this case Lys or Tyr.…”

mentioning

confidence: 99%

Lys- and Tyr-arylamidase activities in serum and brain during the estrous cycle of the rat

Gandarias

Casis²,

Irazusta³

et al. 1989

Acta Endocrinologica

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Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys-and L-Tyr-\g=b\-naphthylamide as substrates. Significant differences were present in the hypothalamus, the pituitary and serum when both substrates were used. However, there were no differences in cortical areas. These results suggest a role for arylamidase activity in the hormonal changes that happen during the estrous cycle of the rat.Neuropeptide degrading enzymes evidently play a role in processing and inactivation of hypothalamic and hypophyseal hormones (1). Arylamidases are among such enzymes, the activities of which can be measured by analysing the hydrolysis of artificial substrates like aminoacyl-ß-naphthylamides (aa-ß-NA; arylamides). Although arylamidases have been implicated in the degradation of several neuropeptides (2), their functional role in the brain is still unknown. The possible endogen¬ ous substrates could be neuropeptides containing the same amino acid at the N-terminal position as arylamides, in this case Lys or Tyr.The hypothalamic-pituitary axis plays a major role integrating endocrine, autonomie and beha¬ vioural responses of animals to various internal and external stimuli. The cyclic hormonal changes during the reproductive cycle enable us to estab¬ lish a comparative study with the enzymatic activ¬ ity probably implicated in their regulation.We report here a study analysing the activity obtained with Lys. and Tyr-ß-Na as substrates during the estrous cycle in serum, the hypothalamus, the pituitary gland and three cortical regions of adult female rats. Materials and MethodsAdult female albino rats (300-350 g) were grouped at estrus, diestrus and proestrus (N = 8 each) verified by vagi¬ nal smear (3). In order to remove plasmatic arylamidases, their brains were perfused from the left cardiac ventricle with saline plus 50 mmol/l of phosphate buffer (pH 7.4) under equithensin anesthesia (2 ml/kg) this included: 42.5 g/1 of chloralhydrate, 0.1621 of Nembutal® 0.3961 of propylene glycol and 21.3 g/1 of magnesium sulphate in distilled water. Blood samples were obtained before per¬ fusion from the left cardiac ventricle and centrifuged to obtain serum which was used as an enzyme and protein source. The brains were quickly removed (less than 60 sec) and cooled in dry ice. Pitutiary gland and tissue sam¬ ples from frontal, parietotemporal, occipital cortex and the hypothalamus were homogenized in 10 mmol/l of TRIS HC1 (pH 7.4) and ultracentrifuged (100 000 X g, 35 min, 4°C) in order to obtain the soluble fraction. The re¬ sulting supernatant was decanted and used for the deter¬ mination of arylamidase activity and proteins. Lys-and Tyr-arylamidase activities (Lys-AR and Tyr-AR) were measured, in triplicate, using Lys-and Tyr-ß-NA as substrates according to the modified method of Greenberg (4): 10 ul of supernatant w...

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“…It is, therefore, impossible to state how many of the peptides investigated in the present study are actually attacked by the en zyme responsible for the cleavage of LH-RH at the Gly6-Leu7-bond. It was stated by Marks [1977] that a neutral endopeptidase present in brain tissue, referred to as cathepsin M, is capable of cleaving LH-RH, substance P and bradykinin at an internal site. He also postu lated that the enzyme responsible for the in activation of oxytocin in the brain is different from cathepsin M, probably because the ring structure of oxytocin prevents the action of peptidases, especially of arylamidases.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the previous extensive use [ Kuhl and Taubert, 1975a;1975b;Kuhl el al., 1976;1977;1978] grading enzymes (arylamidases), the type of inhibition was investigated. The inhibitory ef fect of concentrations of 0-100 fiM Cys-NA on the degradation of LH-RH (5,10 or 20 /jM) by HYP and PIT enzyme preparation during 30 min of incubation is shown in figure 3.…”

Section: Substrates Lh-rh (Pglu-mentioning

confidence: 99%

Enzyme Kinetic Studies and Inhibition by Oligopeptides of LH-RH Degradation in Rat Hypothalamus and Pituitary

Kühl¹,

Sandow²,

Krauss³

et al. 1979

Neuroendocrinology

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The enzyme kinetic parameters of the degradation of luteinizing hormone-releasing hormone (LH-RH) and L-cystine-bis-(4-nitroanilide) (Cys-NA) by rat hypothalamic (HYP) and pituitary (PIT) extracts and the effect of various oligopeptides on the rate of LH-RH inactivation were investigated in vitro. The 105,000 × g supernatant of 1 rat HYP inactivated 57 μg LH-RH during a 30 min incubation (K_m = 12.4 μM,V_max = 2.33 μg LH-RH/mg protein/min), and of one rat anterior PIT, 48 μg LH-RH during 30 min of incubation (K_m = 12.2 μM, V_max = 8.0 μg LH-RH/mg protein/min). The synthetic substrate Cys-NA competitively inhibited LH-RH degradation with a Ki of 8.5 μM in the HYP and 6 μM in the PIT enzyme preparation. Vice versa, LH-RH also competitively inhibited the cleavage of Cys-NA with inhibition constants of 14 μM (HYP) and 15 μM (PIT) indicating that the 2 substrates are probably cleaved by the same enzyme. The most effective inhibitors of LH-RH degradation were found to be angiotensin-related peptides, neurotensin, bradykinin, and bacitracin. A relatively weak effect was obtained with oxytocin, enkephalin and puromycin. It is concluded that endogenous oligopeptides such as angiotensins, neurotensin, bradykinin, etc., may possibly influence LH-RH degradation in the PIT and the HYP. The synthetic substrate Cys-NA may be an appropriate substrate for measuring the activity of an LH-RH-degrading peptidase, which therefore could be classified as arylamidase.

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Conversion and Inactivation of Neuropeptides

Cited by 40 publications

References 165 publications

Vasoactive intestinal polypeptide and the canine cerebral circulation.

Vasoactive intestinal polypeptide and the canine cerebral circulation.

Lys- and Tyr-arylamidase activities in serum and brain during the estrous cycle of the rat

Enzyme Kinetic Studies and Inhibition by Oligopeptides of LH-RH Degradation in Rat Hypothalamus and Pituitary

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