It has been recently reported that 5-hydroxytryptamine (5-HT) increases force of contraction in atrial tissue but not in ventricular tissue. In the present study with trabeculae obtained from non-diseased human hearts, we investigated whether this difference in the contractile responses is specific for 5-HT or is also observed for other substances: calcitonin gene-related peptide (CGRP), angiotensin II, adenosine, somatostatin and acetylcholine. CGRP (10(-9) to 10(-7) M) and angiotensin II (10(-9) to 10(-5) M) caused concentration-dependent increases in force of contraction in atrial trabeculae (up to 36 +/- 8% and 42 +/- 8% of the response to 10(-5) M noradrenaline, respectively). Similar to 5-HT, no effects were observed with CGRP and angiotensin II in ventricular trabeculae. Adenosine (10(-8) to 10(-5) M) and somatostatin (10(-8) to 10(-6) M) caused concentration-dependent negative inotropic effects on baseline atrial contractility (-54 +/- 17% and -51 +/- 25%, respectively), but no response was found on baseline ventricular contractility. Adenosine, but not somatostatin, reduced force of contraction after pre-stimulation with 10(-5) M noradrenaline in atrial tissue and, to a lesser extent, in ventricular tissue. Acetylcholine exhibited a biphasic concentration-response curve in the atrial tissue, consisting of an initial negative inotropic response (10(-9) to 10(-7) M, from 120 +/- 41 mg at baseline to 48 +/- 16 mg at 10(-7) M), followed by a positive inotropic response (10(-6) to 10(-3) M, from 48 +/- 16 mg at 10(-7) M to 77 +/- 15 mg).(ABSTRACT TRUNCATED AT 250 WORDS)