Evidence for contribution of effector organ cellular responses to the biphasic dynamics of heat acclimation

The involvement of cellular processes in the biphasic dynamics of heat acclimation was studied. Key steps in the cholinergic signal transduction pathway for water secretion were measured in the submaxillary gland of acclimating [2-day short-term heat acclimation (STHA) and 30-day long-term heat acclimation (LTHA) at 34 degrees C] or acute heat-stressed (2 h at 40 degrees C) rats in vitro. Both the carbamylcholine (CCh)-induced maximal fractional rate and the total Rb-86(+) efflux, reflecting K+ efflux and water transport, transiently decreased in STHA (P < 0.001). In LTHA, the total K+ efflux increased (P < 0.001), whereas the maximal fractional rate of efflux increased only slightly. During STHA, the density of the high-affinity binding site of the muscarinic receptors (MRs) increased by 50% and their affinity for the muscarinic antagonist [H-3]-N-methylscopolamine decreased transiently by 87%. Basal cytosolic Ca2+ concentration ([Ca2+](i)) decreased (P < 0.05), but the peak CCh-induced [Ca2+](i) increase resembled the control values. In LTHA, MR density continued to increase (100%; P < 0.05), whereas affinity resumed control values. Basal and CCh-induced [Ca2+](i) increases returned to control levels. We conclude that glandular cellular processes follow a biphasic pattern with major apparent changes attributable to events distal to the [Ca2+](i) rise. This was further validated by employing heat stress, which produced qualitatively different effects on the MR profile with a decrease in Rb-86(+) efflux comparable to STHA. Hence, although heat-induced changes in the proximal components of the signal transduction pathway may contribute to altered regulatory span, the predominant apparent cellular effect is on the distal part of the pathway.