Identification of the adenylyl cyclase‐activating 5‐hydroxytryptamine receptor subtypes expressed in the rat submandibular gland

Serotonin (5‐hydroxytryptamine, 5‐HT) has been shown to increase cyclic AMP production in dispersed cell aggregates from the major salivary glands of the rat. The goal of the present study was to identify the 5‐HT receptor subtypes that mediate these effects in rat submandibular glands (SMG). Among the 5‐HT receptor subtypes identified in the rat, 5‐HT4(a,b), 5‐HT6 and 5‐HT7(a,b,c) activate adenylyl cyclase (AC). We used subtype specific primers to screen rat SMG by reverse transcription‐PCR. Results indicate the presence of mRNA for 5‐HT4(b) and 5‐HT7(a) but not for 5‐HT4(a), 5‐HT6 and 5‐HT7(b,c). In dispersed SMG cells, 5‐carboxyamidotryptamine (5‐CT), a 5‐HT7 receptor agonist, stimulated cyclic AMP synthesis with higher potency (EC50=27±5 nM) but lower efficacy than 5‐HT, suggesting a 5‐HT7 component and an additional component in the response to 5‐HT. The 5‐HT7 contribution was further supported by antagonism of the 5‐CT effect by metergoline, a 5‐HT7 antagonist, which exhibited an affinity (Ki=50 nM) similar to that obtained at the cloned 5‐HT7 receptor. In the presence of a maximally effective concentration of 5‐CT, 5‐HT produced an additional increase in cyclic AMP production that was inhibited by the 5‐HT4 receptor antagonist, GR113808, suggesting that the second component of cyclic AMP production is mediated by 5‐HT4 receptors. These findings indicate the presence in rat SMG of both 5‐HT4(b) and 5‐HT7(a) receptors positively coupled to AC. British Journal of Pharmacology (2000) 130, 104–108; doi:10.1038/sj.bjp.0703303