Anorectic Activity of Prostaglandin Precursors

Abstract

1 Intraperitoneal and intragastric (i.g.) administration of prostaglandin precursors arachidonic (2 mg, 15 mg/kg, i.p.; 30 mg/kg, i.g.), linolenic (100 mg/kg, i.p.; 200 mg/kg, i.g.) and linoleic (15, 100 mg/kg, i.p.; 100 mg/kg, i.g.) acids to 22 h food‐deprived rats inhibits food intake. 2 This anorexia is similar to that induced by prostaglandin F2α (1 mg/kg, i.p.). 3 At anorectic doses these fatty acids do not cause pyrexia, in fact arachidonic acid causes hypothermia. 4 Prior treatment with indomethacin (15 mg/kg) and paracetamol (50 mg/kg) specifically reverses the anorexia and the behavioural satiety induced by the three fatty acids, while not affecting prostaglandin F2α‐induced suppression of food intake. 5 Results of the present experiments suggest that both physiological and pharmacological modification of appetite could be brought about through an effect on prostaglandin generating systems.

SOME OBSERVATIONS ON THE ANORECTIC ACTIVITY OF PROSTAGLANDIN F2α

“…Injection of a prostaglandin antagonist into the aadrenoceptor loci increased feeding when given alone and antagonized the hypophagia induced by prostaglandin E, on prior injection (Martin, Baile, Webb & Kingsbury, 1972;Baile & Martin, 1973;Baile, Martin, Forbes, Webb & Kingsbury, 1974 (Holmes & Horton, 1968), and furthermore F prostaglandins are the only ones that can be synthesized by rat brain (Feldberg, 1974). A preliminary investigation on food intake when prostaglandin F2a was injected into the cerebroventricular system has been reported earlier (Doggett & Jawaharlal, 1975). The present paper is an extension of our earlier study.…”

“…Prostaglandins have been shown to have many other actions which affect food intake. They cause irritation and pain (Collier & Schneider, 1972); when injected into the ventricular system of the brain they produce hyperthermia (Milton & Wendlandt, 1971;Doggett & Jawaharlal, 1975). Therefore it is possible that the anorectic activity of prostaglandins is only secondary to those actions.…”

“…A number of other reasons also exclude hyperthermia as the cause of their anorectic activity. There is no correlation between their anorectic and hyperthermic activities Doggett & Jawaharlal, 1975). Injection of prostaglandins peripherally cause anorexia and hypothermia ( Figure 6).…”

“…Studies from a number of laboratories in the last few years (Horton, 1964;Scaramuzzi et al, 1971;Doggett & Jawaharlal, 1975) have implicated prostaglandins in regulation of food intake in a number of species. Prostaglandins have been shown to have many other actions which affect food intake.…”

“…(Figure 5). Effect ofprostaglandin F2a on body temperature Prostaglandin F2a when injected intracerebroventricularly in rats causes hyperthermia and anorexia (Doggett & Jawaharlal, 1975) so the possibility exists that its anorectic activity is secondary to its hyperthermic effect. Intraperitoneal injection of 0.5 and 1 mg/kg body weight of prostaglandin F2a to rats deprived of food for 22 h produced whole body hypothermia ( Figure 6) which was maximal at 90 min after administration.…”