1. The systemic plasminogen activator response has been examined after intravenous infusion of the following peptides related to neurohypophyseal hormones in approximately equimolar dosages into informed, consenting human volunteer subjects: (a) the natural nonapeptides: lysine- and arginine-vasopressin, oxytocin and arginine-vasotocin, (b) the N- and C-terminal tripeptide fragments of vasopressin and (c) four vasopressin analogues without pressor activity, altered at the N-terminus, the disulphide bridge and/or sequence position 8 in the C-terminal tripeptide. In addition, angiotensin II and adrenaline were infused.
2. It was observed that some of the cyclic nonapeptides resulted in high and prolonged increases in amounts of plasminogen activator in venous blood, in the following order, both for amplitude and duration: 1-desamino-6-monocarba-[8-d-arginine]-vasopressin > 1-desamino-[8-d-arginine]-vasopressin ≫ arginine-vasopressin = lysine-vasopressin > Nα-glycyl-glycyl-glycyl-lysine-vasopressin.
3. No plasminogen activator responses followed infusions of vasopressin tripeptide fragments, oxytocin, angiotension II, 1-desamino-[8-N-MeArg]-vasopressin or 9-desglycineamide-lysine-vasopressin octapeptide.
4. Mole for mole, the four most active substances were approximately two orders of ten more potent than adrenaline by amplitude comparison alone.
5. Intra-arterial adrenaline, in one-tenth the systemic dose, stimulated a release of plasminogen activator from the infused local vascular bed only, This did not occur with equivalent doses of arginine-vasopressin and 1-desamino-[8-d-arginine]-vasopressin.
6. It is concluded that plasminogen activator release arising from catecholamine-responding and vasopressin-responding receptors are both molecule-specific and different in anatomical location. The molecular structural requirements for triggering the latter hypothetical receptor type and potential clinical applications are discussed.