Identification of plasminogen activator releasing activity in the neurohypophysis

Abstract

Vasopressin (AVP) and some of its synthetic analogues, for example 1 desamino 8-D-AVP (DDAVP), induce plasminogen activator (PA) release in vivo. It has been proposed that this occurs via the release from the central nervous system of a plasminogen activator releasing hormone (PARH). The present study shows that a crude extract of bovine posterior pituitary, but not of the anterior pituitary or of the hypothalamus, induces a marked increase of circulating PA in anaesthetized rats. PA release appears to be caused by AVP because no other PA releasing activities could be identified in or isolated from the extract. In addition, no PA-releasing activity was found in extracts of pituitary glands of rats congenitally deficient in vasopressin. The following experiments did not reveal central nervous system involvement in the PA-release caused by AVP or DDAVP. Perfusion of isolated organs (rat heart and rat liver) with AVP resulted in PA-release. In squirrel monkeys, comparable PA levels were found in the venous return following intrafemoral or intracarotid injection of AVP. Moreover, when plasma obtained 2 min following AVP or DDAVP injection was transfused to a receiving animal no PA release was observed. Thus our present findings do not support the hypothesis that the fibrinolytic response to AVP is mediated by the release of a specific peptide hormone from the central nervous system.

Influence of protein C activation on blood coagulation and fibrinolysis in squirrel monkeys.

“…T-TM complex has been demonstrated to be a very potent activator of PC devoid ofclotting and plateletactivating activities (3,10,15,16) The possibility that the squirrel monkey is a poor responder to PA releasing agents is excluded. Previous investigations by our laboratory (17) have indeed shown that infusion of known stimulators of PA release, such as vasopressin or DDAVP, induce a marked fibrinolytic response in the squirrel monkey (up to threefold increase in the plasma levels of PA). Furthermore, we demonstrated that the increase of circulating PA is mainly due to the release of tissue-type PA.…”

Fibrinolytic Responses to 1-Desamino-8-<i>D</i>-Arginine-Vasopressin in Patients with Congenital Nephrogenic Diabetes insipidus

“…Cash et al [27] hypothesized that vasopressin-like molecules may be hu moral messengers acting on a cephalic center, which may in turn release a second messenger that stimulates the endothelial cells indirectly. However, this putative sec ond messenger has not been identified in bovine pituitary and hypothalamic extracts [28]. In addition, patients with hypopituitarism resulting from surgical adenohypophysectomy respond normally to desmopressin [29,30], In a study with anephric patients, it was demonstrated that a functioning kidney is not required for the effect of D D A V P on the fibrinolytic activity o f the blood [31].…”

Tissue-Type Plasminogen Activator

“…Cash [23] has suggested the existence of neuro-humoral regulation, by a hormone ('plasminogen acti vator releasing hormone'; PARH) which con trols the release of the activator by the endo thelial cells. However, this hormone has not been identified in extracts of bovine pituitary or hypothalamus [24], From their results ob-tained with the infusion of bovine protein C in dogs, Comp and Esmon [25] have sug gested that activated protein C may play a role in the release of t-PA in vivo. These results have not been confirmed in the squir rel monkey following the infusion of human protein C [26].…”