Enzymatic activity of rat submandibular gland kallikrein released into blood

Berg, Torill; Johansen, Liv; Nustad, Kjell

doi:10.1152/ajpheart.1985.249.6.h1134

Cited by 13 publications

(25 citation statements)

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“…Some of these polypeptides, such as renin, NGF, EGF in mice [lo, 11, 16-18, 211 and kallikrein in rat [14] are also released from the gland into the bloodstream following stimulation by catecholamines. Similarly, we observed the appearance of the hexapeptide in the blood of male rats following the injection of the adrenergic agonist agent.…”

Section: Discussionmentioning

confidence: 99%

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Rougeot

Rosinski‐Chupin

Njamkepo

et al. 1994

European Journal of Biochemistry

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The amino acid sequence of submandibular rat 1 (SMR1) protein, deduced from its cDNA sequence, led to the prediction that the SMR1 gene encodes a hormone‐like precursor [Rosinski‐Chupin, I., Tronik, D. & Rougeon, F. (1988) Proc. Natl Acad. Sci. USA 85, 8553–8557]. SMR1 contains an N‐terminal putative secretory signal sequence and a tetrapeptide (QHNP), located between dibasic amino acids which constitute the most common signal for prohormone processing. We have isolated and characterized from the male rat submandibular gland and its secretions three structurally related peptides, namely an undecapeptide (VRGPRRQHNPR), a hexapeptide (RQHNPR) and a pentapeptide (QHNPR) generated from SMR1 by selective proteolytic cleavages at pairs of arginine residues. The biosynthesis of these peptides is subjected to distinct regulatory pathways depending on the organ, sex and age of the rat. Furthermore, the peptides are differentially distributed in the submandibular gland and in resting or epinephrine‐elicited submandibular salivary secretions, suggesting distinct proteolytic pathways for their maturation. The undecapeptide is generated in the gland of both male and female rats, but under basal conditions it is only released into the saliva in male animals. The hexapeptide is produced in large amounts in the gland of adult male rats and released into the saliva in both resting and stimulated conditions. The pentapeptide appears only in the male saliva and is present mostly under stimulated conditions. In addition, administration of epinephrine induces the release of the hexapeptide from the submandibular gland into the bloodstream. The evidence indicates that the rat submandibular gland can function as a dual exocrine and endocrine organ for the SMR1‐derived hexapeptide, as has been reported for nerve growth factor, epidermal growth factor, renin and kallikrein. Although the biological activities of the SMR1‐derived peptides are not yet known, their high production and adrenergic‐induced release only into the saliva and bloodstream of adult male rats, suggest a physiological involvement in some male‐specific processes.

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Section: Discussionmentioning

confidence: 99%

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Rougeot

Rosinski‐Chupin

Njamkepo

et al. 1994

European Journal of Biochemistry

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“…This result suggests that there was a little release of tonin from the resting gland, but tonin was evidently released from the submaxillary gland into the systemic circulation by adrenergic stimulation, as is kallikrein. 29 ' 30 Although we used critically high doses of norepinephrine to stimulate the tonin secretion instead of electrical stimulation of the autonomic nervous system, the stimulation to the submaxillary gland seemed to be effective because there was also a significant increase in saliva, which contained a large amount of tonin (data not shown). Thus, tonin is released from the submaxillary gland into the circulation and is complexed with a,M.…”

Section: Discussionmentioning

confidence: 99%

Formation of angiotensin II by tonin-inhibitor complex.

et al. 1988

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SUMMARY Enzymatic activity of tonin-o^-macroglobulin complex was studied in vitro and in vivo, using an immunoimmobilization technique. Tonin-ai-macroglobulin complex, which was immunologically immobilized by anti-a r macroglobulin antibody covalently coupled to agarose gels, could quantitatively hydrolyze angiotensin I and synthetic tridecapeptide renin substrate to form angiotensin II. However, the solid-phase antibody-bound tonin-a,-macroglobulin complex could not hydrolyze the plasma protein renin substrate. Phenylmethylsulfonyl fluoride, a serine protease inhibitor, inhibited both free tonin and the solid-phase antibody-bound tonin-a|-macroglobulin complex. The hydrolytic activity of the solid-phase antibody-bound tonin-«,-macroglobulin complex against angiotensin I was not inhibited by soybean trypsin inhibitor (molecular weight, 23,000), a potent inhibitor of free tonin. Taken together, these results suggest that tonin bound to c^-macroglobulin keeps the active site intact and that inhibition of the enzyme activity is due to a steric hindrance. When 500 /xl of tonin was administered intravenously to rats, the immunoimmobilization method was used to show that the tonin-a r -macroglobulin complex in the plasma formed angiotensin II. Thus, the tonin-a r macroglobulin complex in the plasma may be linked to some forms of hypertension through angiotensin II formation. (Hypertension 11: 63-70, 1988) KEY WORDS • tonin immunoimmobilization angiotensin I • angiotensin II • a r -macroglobulin

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“…8 - 9 The submandibular gland of the rat is extremely rich in kallikrein, which is released into not only saliva but also the vascular compartment. 10 - 11 Kallikrein released into blood remains sufficiently active to induce vasodiiatation in the resting gland when kinin degradation is partially blocked by captopril, a kininase II converting enzyme inhibitor (CEI). 6 - 10 Pretreatment with antibodies against bradykinin abolished this effect of CEI, suggesting that this vasodilatory response is mediated by kinins.…”

Section: P Otent Vasodilator Kinins Acting As Paracrinementioning

confidence: 99%

“…10 - 11 Kallikrein released into blood remains sufficiently active to induce vasodiiatation in the resting gland when kinin degradation is partially blocked by captopril, a kininase II converting enzyme inhibitor (CEI). 6 - 10 Pretreatment with antibodies against bradykinin abolished this effect of CEI, suggesting that this vasodilatory response is mediated by kinins. 6 Stimulation of the sympathetic nerve causes vasoconstriction followed by poststimulatory vasodiiatation in the gland.…”

Section: P Otent Vasodilator Kinins Acting As Paracrinementioning

confidence: 99%

“…Its venous blood has a higher concentration of kallikrein than arterial blood, 10 -11 and part of it is in an enzymatically active form. 10 In nephrectomized rats, partial inhibition of kinin destruction by CEI results in increased glandular blood flow that is blocked by antibodies against kinins. 6 Furthermore, immediately after stimulation of the submandibular sympathetic nerve, kallikrein is released and gains access to the vascular compartment.…”

Section: Typical Recordings Of Submandibular Gland Blood Flow In Respmentioning

confidence: 99%

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Role of kinin in regulation of rat submandibular gland blood flow.

et al. 1989

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In tissues rich in kalUkrein, vasodilator kinins, acting as paracrine hormones, may play a role in the local regulation of blood flow. We studied the role of kinins in the regulation of blood flow in the rat submandibular gland using a kinin analogue with antagonistic properties, [DArg°]Hyp 3 -Thi iS [DPhe 7 ]bradykinin. When infused into the carotid artery (20 jtg/min/rat), this antagonist blocked the effect of bradykinin (25-250 ng/kg, intracarotid injection) on glandular blood flow. In nephrectomized rats, the antagonist also blocked the increase in glandular blood flow caused by enalaprilat, a kininase II converting enzyme inhibitor. At a dose of 20 /tg/min/rat, the antagonist produced no detectable change in basal glandular blood flow; however, at a higher dose (100 /ig/min/rat), it caused a significant decrease (/?<0.001). In eight of 10 rats, blood flow decreased by 75% or more; this effect was not blocked by the cv-adrenergic receptor antagonist phentolamine. After antagonist infusion was stopped, blood flow returned toward normal. Sympathetic nerve stimulation of the gland induced vasoconstriction followed by poststimulatory vasodiiatation. In rats displaying severe vasoconstriction after the antagonist, postsympathetic vasodiiatation was abolished even when stimulation was performed after the antagonist infusion had been stopped and blood flow returned toward normal. Although a direct vasoconstrictor effect of the kinin antagonist cannot be completely ruled out, these data suggest that, in the rat submandibular gland, kinins may play a role in regulation of basal blood flow and vasodiiatation after converting enzyme inhibitor or sympathetic stimulation. (Hypertension 1989;14:73-80) P otent vasodilator kinins, acting as paracrine hormones, may participate in local regulation of blood flow, possibly through activation of endothelium relaxing factor, 1 particularly in organs rich in kallikrein, 2 -7 but their role has been a subject of much controversy. 8 -9 The submandibular gland of the rat is extremely rich in kallikrein, which is released into not only saliva but also the vascular compartment. -11 Kallikrein released into blood remains sufficiently active to induce vasodiiatation in the resting gland when kinin degradation is partially blocked by captopril, a kininase II converting enzyme inhibitor (CEI). Received September 19, 1988; accepted January 23, 1989. mediated by kinins. 6 Stimulation of the sympathetic nerve causes vasoconstriction followed by poststimulatory vasodiiatation in the gland. 11- 12 We have shown that this vasodiiatation is accompanied by simultaneous release of kallikrein and kinins into the vascular compartment of the gland. 7 -10 -11 Both the poststimulatory vasodiiatation and the release of kallikrein were abolished by a-adrenergic (phentolamine) but not by /3-adrenergic (propranolol) blockade.11 These studies suggest that the kallikreinkinin system may play a role in regulation of basal submandibular gland blood flow as well as in the vasodiiatation that follows CEI ad...

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Enzymatic activity of rat submandibular gland kallikrein released into blood

Cited by 13 publications

References 0 publications

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Formation of angiotensin II by tonin-inhibitor complex.

Role of kinin in regulation of rat submandibular gland blood flow.

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