Intrahypothalamic injections of prostaglandins and prostaglandin antagonists and feeding in sheep.

Abstract Prostaglandins are thought to play a role in neural transmission, and we have considered the possibility that they may act as feedbacks from fat depots to the central nervous system for maintenance of energy balance. To test for direct prostaglandin effects on the hypothalamus, sheep were implanted with guides directed toward the hypothalamus. With loci in the medial and anterior hypothalamus in which L-norepinephrine injections elicited feeding, prostaglandin E 1 (14 and 28 nmol) reduced spontaneous feeding for .5 to 1h. Prostaglandin E 2 similarly injected did not affect feeding. Loci in the lateral anterior hypothalamus in which L-norepinephrine injections did not elicit feeding when injected with prostaglandin E 1 ; but not E 2 , increased feed intake for up to 60min. Of the prostaglandin antagonists tested (polyphloretin phosphate, oxaprostynoic acid, and SC 19220), only the first had the predicted effect of increasing feed intake in the loci selected for the I-norepinephrine-bound feeding. Approximately 6 nmol (100 μ ) of polyphloretin phosphate resulted in the maximum response. An injection of 6 nmol of polyphloretin phosphate 30min before 14 nmol prostaglandin E 1 into loci in which L-norepinephrine elicited feeding resulted in feeding greater than control and much greater than that following carrier and prostaglandin E 1 injections. These experiments show that prostaglandin E 1 , but not E 2 , injected into the hypothalamus decreases feeding in medial and anterior loci which show l-norepinephrine-bound feeding, but it increases feeding in more lateral loci and possibly the effects of both endogenous and exogenous prostaglandin can be blocked by polyphloretin phosphate. The possibility remains that prostaglandins play a role in maintenance of energy balance.

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