Microelectrophoresis of PGE1 onto single units in the rabbit hypothalamus

Abstract

Prostaglandin E1 (PGE1) when micro-injected into the preoptic anterior hypothalamus (PO/AH) of conscious rabbits is a potent pyrogenic agent. We have investigated the action of PGE1 on the activity of single units of the PO/AH area using the microelectrophoretic technique. One hundred and thirty-eight PO/AH units were tested both for their response to changes in local PO/AH temperature and for their response to PGE1 application. Less than 9.0% of the total population of units tested showed any response to PGE1 application. When present, the response was invariably one of mild facilitation. No specific unit type (thermally sensitive or insensitive) appeared to be selectively affected by PGE1. Thus, the proportion of units affected by PGE1 was constant at 8-10% for warm-sensitive, cold-sensitive, or thermally insensitive units. There was no evidence to support an antagonistic role for PGE1 on the effects on norepinephrine on PO/AH units. On the basis of these results, we cannot predicate any simple neuronal basis for the action of PGE1 in producing fever in conscious rabbits. However, it is suggested that the action of PGE1 might be the modulation of presynaptic release of neurotransmitter onto the units of the PO/AH area.

Thermal and PGE2 sensitivity of the organum vasculosum lamina terminalis region and preoptic area in rat brain slices.

“…The present results on POA neurones are somewhat different from these previous ones, in which predominantly facilitatory responses of POA neurones in vitro (Watanabe et al 1987) or the low sensitivity to PGE2 in POA neurones in vivo (Stitt et al 1975) were demonstrated. However, the application of PGE2 in unphysiologically high concentrations (e.g.…”

“…Since it has been proposed that warm-sensitive and cold-sensitive neurones facilitate heat defence responses and cold defence responses of thermoregulation, respectively (Boulant, Curras & Dean, 1989;Hori, 1991), these changes in POA thermosensitive neurones are appropriate in explaining the changes in thermoregulatory responses during the rising phase of fever, i.e., inhibition of heat defence responses and facilitation of cold defence responses. However, no studies on the direct application of PGE2 on POA neurones have revealed a consistent relationship between the responsiveness of POA neurones to PGE2 and temperature (Stitt et al 1975: Boulant & Scott, 1986Watanabe et al 1987;Morimoto et al 1988). In confirmation with these findings, no correlation between the responsiveness of POA neurone to PGE2 and temperature was found in the present study which was undertaken in a more carefully controlled experimental condition than in the previous ones.…”

“…The hypothalamus, particularly the preoptic area (POA), has long been proposed as the primary site of action of EPs/IL-1 (Hori, Shibata, Nakashima, Yamasaki, Asami, Asami & Koga, 1988). However, the lack of evidence showing the actual entry of blood-borne EPs/IL-1 into the brain (Dinarello, Weiner & Wolff, 1978) and the lack of a consistent relationship between the thermosensitivity and the PGE2 responsiveness of POA neurones (Stitt & Hardy, 1975;Boulant & Scott, 1986) do not support this, although EPs/IL-1, which is synthesized in the brain, might contribute, at least partly, to the development of fever (Fontana, Weber & Dayer, 1984;Hori et al 1988; Nakashima, Hori, Mori, Kuriyama & Mizuno, 1989).…”

Effects of prostaglandin D2 on the activity of hypothalamic neurons in the rat.

“…Antagonism of the NA response of cerebellar Purkinje neurons by PGE has been reported (SIGGINS et al, 1971), but no such effect has been observed on hypothalamic neurons (STIT and HARDY, 1975;JELL and SWEATMAN, 1977). The present experiments revealed modulation by PGD2 of both the NA response and the ACh responses of LPOA neurons.…”

“…Direct effects on neuronal activity in the hypothalamus were mainly excitatory and the incidence of responsive neurons ranged from 9 to 83% (JELL and SWEATMAN, 1977;POULAIN and CARETTE, 1974;STIT and HARDY, 1975). In contrast, the effects of PGD2 on the CNS have received less attention.…”