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Intrahypothalamic Injections of Prostaglandins and Prostaglandin Antogonists and Feeding in Sheep

¹ Smith Kline & French Laboratories, West Chester, Pennsylvania 19380
and² University of Pennsylvania, Philadephia 19104

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 medal and anterior hypothalamus in which 1-norepinephrine injections elicited feeding, prostaglandin E₁ (14 and 28 nmol) reduced spontaneous feeding for .5 to 1 h. Prostaglandin E₂ similarly injected did not affect feeding. Loci in the lateral anterior hypothalamus in which 1-norepinephrine injections did not elicit feeding when injected with prostaglandin E₁; but not E₂, increased feed intake for up to 60 min. 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 1-norepine-phrine-bound feeding. Approximately 6 nmol (100 µ) of polyphloretin phosphate resulted in the maximum response. An injection of 6 nmol of polyphloretin phosphate 30 min before 14 nmol prostaglandin E₁ into loci in which 1-norepinephrine elicited feeding resulted in feeding greater than control and much greater than that following carrier and prostaglandin E₁ injections. These experiments show that prostaglandin E₁, but not E₂, injected into the hypothalamus decreases feeding in medial and anterior loci which show 1-norep-nephrine-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.

³ While on leave from the Department of Animal Phsysiology and Nutrition, University of Leeds, Leeds, England.