M. Dunér-Engström

Effects of VIP, PHM and substance P on blood vessels and secretory elements of the human submandibular gland

The effects of the neuropeptides VIP, PHM and substance P (SP) on vascular smooth muscle tone, K+ secretion from exocrine elements and tissue content of cyclic AMP (cAMP) in the human submandibular gland were studied in vitro. All three peptides caused relaxation of noradrenaline contracted human submandibular arteries at nM concentrations. SP was slightly more active than VIP and PHM which had a similar potency as vasodilators. Only carbachol but not VIP, PHM or SP stimulated K+ secretion from exocrine elements of the human submandibular gland. Principally similar in vitro effects on K+ secretion were obtained on the cat submandibular gland, but in the rat not only carbachol but also SP stimulated K+ secretion. VIP and PHM increased cAMP production of exocrine elements in the human submandibular gland in nM concentrations. VIP was about 5-fold more potent than PHM with regards to cAMP production. In conclusion, VIP, PHM and SP relaxed human submandibular arteries in vitro. Both VIP and PHM stimulated cAMP production in glandular tissue but none of the three peptides induced K+ secretion from human submandibular gland tissue. This suggests that, in contrast to the situation in the rat, SP does not cause watery salivation in man, while VIP and PHM may modulate protein e.g. amylase content of the saliva.

Interactions Between the Neuromodulator Adenosine and the Classic Transmitters

The present studies give examples of three types of interactions between adenosine and classic neurotransmitters. First, the transmitter substances may influence the amount of adenosine formed locally. Depolarizing stimuli have long been known to increase the amount of adenosine released from peripheral tissues as well as brain tissue in vitro and in vivo. In addition, the magnitude of this response, and the formation of adenosine induced by hypoxia, may be altered by other transmitters, such as opioids, in ways that are still undefined.

Formation and Actions of Adenosine in the Rat Hippocampus, with Special Reference to the Interactions with Classical Transmitters

Adenosine and related compounds can probably play a transmitter or cotransmitter role at least in some tissues (e.g., Burnstock, 1985). However, this seems to be rare and the major functional role of adenosine not only in the periphery but also in the nervous system appears to be that of a modulator. Adenosine is released not only from nerve terminals but also from cell bodies and from glial cells or endothelial cells lining the cerebral blood vessels. Besides its role in blood-flow regulation, adenosine clearly plays a role in modulation of nervous activity, pre- and postjunctionally.

Mechanisms of Adenosine Action

As clearly shown during this symposium adenosine may play an important modulatory role in several cells and tissues (see figure 1). Most of the effects of adenosine are mediated via cell surface receptors which can be grouped into two major categories A1 and A2. The pharmacological characterization of these two receptor types has been dealt with extensively elsewhere — the aim of this paper is instead to briefly discuss some aspects of the signalling from these receptors.

Mechanisms of Inhibition of Transmitter Release by Adenosine Analogs

ABSTRACT Adenosine receptors similar to A1 receptors mediate inhibition of the release of several neurotransmitters in the rat hippocampus. A G-protein, that is probably not a pertussis toxin substrate, is involved. Inhibition of cyclic AMP formation is usually not an important mechanism, neither is an interaction with protein kinase C. Adenosine effects are different from autoreceptor effects in that they are less sensitive to 4-AP and are similar to the effects of ω-conotoxin.