1. The mechanism of
5-hydroxytryptamine (5-HT)-induced
tachycardia is species-dependent and is mediated directly or indirectly either by '5-HT1-like' (cat), 5-HT2 (rat, dog) or 5-HT3 (rabbit) receptors, or by an action similar to
tyramine (guinea-pig). The present investigation is devoted to the analysis of the positive chronotropic effect of
5-HT in the
pentobarbitone-anaesthetized pig. 2. Intravenous bolus
injections of
5-HT (3, 10 and 30 micrograms kg-1) in pigs resulted in dose-dependent increases in heart rate of 24 +/- 2, 38 +/- 3 and 51 +/- 3 beats min-1, respectively (n = 39). Topical application of a high concentration of
5-HT (150 micrograms kg-1 in 5 ml) on the right atrium was also followed by
tachycardia (38 +/- 6 beats min-1, n = 4). 3. A number of drugs which antagonize responses mediated by different
5-HT receptors--
phenoxybenzamine,
methiothepin,
metergoline,
methysergide and
mesulergine ('5-HT1-like' and 5-HT2 receptors),
ketanserin,
cyproheptadine,
pizotifen and
mianserin (5-HT2 receptors), and
MDL 72222 and
ICS 205-930 (5-HT3 receptors)--did not attenuate the chronotropic responses to
5-HT. 4. The 5-HT-induced
tachycardia was also not affected by antagonists at alpha- and beta-
adrenoceptors,
muscarinic, nicotinic,
histamine and
dopamine receptors, and
calcium channels. 5. Selective inhibitors of 5-HT-uptake,
indalpine and
fluvoxamine, themselves increased porcine heart rate and facilitated 5-HT-induced
tachycardia both in magnitude and in duration. 6. A number of putative selective agonists at '5-HT1-like' receptors or their possible subtypes (5- carboxamidotryptamine (5-CT), 8-hydroxy-24di-N,N-n-propylamino)
tetralin (8-OH-DPAT),
BEA 1654 and
RU 24969), or at 5-HT3 receptors (2-methyl-5-HT), elicited no or only a weak tachycardiac response in the pig.
RU 24969, but not 8-
OH-DPAT, seemed to potentiate the responses to 5-HT, whereas 5-CT slightly inhibited these responses. 7. It was concluded that the
tachycardia induced by 5-HT in the pig does not involve the receptors for some common
neurotransmitter substances but may be mediated by a new
5-HT receptor type that is clearly different from '5-HT1-like', 5-HT2 or 5-HT3 receptors.