Thermolytic salivation, substance P and kinins in rats

Abstract

In the heat, rats produce a large flow of saliva that they spread on their fur. We have tested whether substance P (SP) is involved in this response by using RP 67580, a NKj tachykinin receptor antagonist, in normal and in kininogen-deficient rats. In anaesthetized rats, the sialogogic effect of SP (1 and 5 μg.kg^-1 iv) was inhibited by RP 67580 (50 to 2500 μg.kg^-1 iv). SP (5 μg.kg^-1 iv) did not modify the vascular permeability to ¹²⁵I-labelled albumin in submaxillary glands but increased this permeability in periglandular soft tissues and in the ears. This effect was suppressed by RP 67580 (50 to 2500 μg.kg^-1 ip).

Unanaesthetized normal male Wistar rats were exposed to ambient temperatures of 26°C (thermoneutral range) or 36°Cfor one hour. After this time period, a loss of body weight was observed. The thermolytic water loss reached 2% of body weight. This body weight loss was reduced by atropine (3 mg.kg¹ ip) or RP 67580 (50 to 2500 μg.kg^-1 ip). The submaxillary glands were swollen and accumulated labelled albumin. This accumulation was reduced by atropine but was not affected by RP 67580. An extravasation of labelled albumin occurred in periglandular tissues. This accumulation was not modified by atropine which induced a large oedema of the soft tissues. Protein extravasation was suppressed by RP 67580 (2500 μg.kg^-1) which did not modify or increased the volume of the oedema. In kininogen-deficient rats exposed to 36°C for one hour, the water loss was reduced by atropine and suppressed by a combination of atropine and RP 67580. Body temperature was increased by atropine and RP 67580. Atropine induced a large periglandular oedema which developed without an extravasation of labelled albumin. RP 67580 had no effect on this oedema.

Taking the body weight loss as a measure of the flow of saliva, we concluded that heat-induced salivation would depend on a stimulation of submaxillary glands by acetylcholine and tachykinins. The increase in vascular permeability observed in periglandular soft tissues would result from bradykinin formation and tachykinin release. The mechanism of the development of the periglandular oedema remains unclear.

Key Words:

• Salivary glands
• tachykinin
• substance P
• kinins
• thermoregulation
• NK₁ receptor
• RP 67580